Sucrose activates human taste pathways differently from artificial sweetener

Frank, Guido K.W.; Oberndorfer, Tyson A.; Simmons, Alan N.; Paulus, Martin P.; Fudge, Julie L.; Yang, Tony T.; Kaye, Walter H.

doi:10.1016/j.neuroimage.2007.10.061

Cited by 274Biochemical Analysis and Sensing TechniquesOlfactory and Sensory Function StudiesNeurotransmitter Receptor Influence on Behavior

Sucrose activates human taste pathways differently from artificial sweetener

Frank, Guido K.W., Oberndorfer, Tyson A., Simmons, Alan N., Paulus, Martin P., Fudge, Julie L., Yang, Tony T., Kaye, Walter H.·2008·NeuroImage

DOI 10.1016/j.neuroimage.2007.10.061

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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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Human imaging studies have shown that tasting palatable foods activated the insula and midbrain areas.
“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]
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.
“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]
When normal weight women tasted sucrose, both insula and DA midbrain areas activated, whereas sucralose only activated the insula.
“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 humans, tasting palatable foods activated the insula and midbrain areas.
“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]
Human imaging studies have shown that tasting palatable foods activated the insula and midbrain areas.
“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

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Altered processing of sweet taste in the brain of diet soda drinkers
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“Frank and colleagues [15] reported less activation of reward areas in response to the noncaloric sucralose stimulus relative to the caloric sucrose, and while Chambers et al.”
Sugar reduction without compromising sensory perception. An impossible dream?
Hutchings, S. C., Low, J. Y. Q., & Keast, R. (2018) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2018.1450214 · Cited by 143 · see citing works
“Similarly, in another study by Frank et al. (2008), researchers found that both caloric sugar and NNS were able to activate the primary taste pathway in the brain, but only caloric sugars were able to activate a significant response from brain regions involved in the brain’s reward pathway.”
Background
Physiological mechanisms by which non-nutritive sweeteners may impact body weight and metabolism
Burke, M. V., & Small, D. M. (2015) · Physiology & Behavior · doi:10.1016/j.physbeh.2015.05.036 · Cited by 132 · see citing works
“found that tasting sucrose and sucralose activated common taste pathways, but absolute brain response after sucrose was stronger than for sucralose [112].”
Background
Fructose-containing caloric sweeteners as a cause of obesity and metabolic disorders
Tappy, L. (2018) · Journal of Experimental Biology · doi:10.1242/jeb.164202 · Cited by 126 · see citing works
“…activates brain regions (anterior insula, Jo u rn al o f Ex p er im en ta lB io lo g y frontal operculum, striatum and anterior cingulate) that are involved in sweet taste perception, but only sucrose simultaneously activates the dopaminergic reward pathways in healthy women (Frank et al., 2008).”
Background
Males and females show differential brain activation to taste when hungry and sated in gustatory and reward areas
Haase, L., Green, E., & Murphy, C. (2011) · Appetite · doi:10.1016/j.appet.2011.06.009 · Cited by 118 · see citing works
“…Van De Moortele, MacLeod, Le Bihan, & Faurion, 2001; de Araujo, Kringelbach, Rolls, & McGlone, 2003; Faurion et al., 1999; Francis et al., 1999; Frank et al., 2008; Kringelbach et al., 2003; Kringelbach, de Araujo & Rolls, 2004; O'Doherty et al., 2001; Zald et al., 2002) and fMRI experiments…”
Result
Oral carbohydrate sensing and exercise performance
Jeukendrup, A. E., & Chambers, E. S. (2010) · Current Opinion in Clinical Nutrition and Metabolic Care · doi:10.1097/mco.0b013e328339de83 · Cited by 118 · see citing works
The Sweet Taste of Success
Hagger, M. S., & Chatzisarantis, N. L. D. (2012) · Personality and Social Psychology Bulletin · doi:10.1177/0146167212459912 · Cited by 115 · see citing works
“It is important to note that the activation of these regions is confined to solutions containing sugar and does not occur in response to artificial sweetener; no activation of the ACC and ventral striatum has been observed in participants rinsing their mouths with a solution containing a noncaloric artificial sweetene…”
Background
Carbohydrate in the mouth enhances activation of brain circuitry involved in motor performance and sensory perception
Turner, C. E., Byblow, W. D., Stinear, C. M., & Gant, N. (2014) · Appetite · doi:10.1016/j.appet.2014.05.020 · Cited by 110 · see citing works
“Other neuroimaging investigations have shown that carbohydrate solutions produce increased cortical activation when compared with equivalently sweet artificially sweetened placebo solutions (Frank et al., 2008; Haase, Cerf-Ducastel, & Murphy, 2009).”
BackgroundResult
Consumption of caloric and non-caloric versions of a soft drink differentially affects brain activation during tasting
Smeets, P. A. M., Weijzen, P. L. G., de Graaf, C., & Viergever, M. A. (2010) · NeuroImage · doi:10.1016/j.neuroimage.2010.08.054 · Cited by 106 · see citing works
“Nevertheless, neuroimaging studies have shown different brain responses to solutions of sugars and non-caloric sweeteners inwater (Frank et al., 2008; Smeets et al., 2005).”
Influential
Bridging Exercise Science, Cognitive Psychology, and Medical Practice: Is “Cognitive Fatigue” a Remake of “The Emperor’s New Clothes”?
Pattyn, N., Cutsem, J. V., Dessy, E., & Maîresse, O. (2018) · Frontiers in Psychology · doi:10.3389/fpsyg.2018.01246 · Cited by 106 · see citing works
“, 2012; Hagger and Chatzisarantis, 2013) which can have rewarding properties (Frank et al., 2008; Van Cutsem et al., 2017a).”
Background
Frontostriatal and behavioral adaptations to daily sugar-sweetened beverage intake: a randomized controlled trial
Burger, K. S. (2017) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.116.140145 · Cited by 99 · see citing works
A caffeine-maltodextrin mouth rinse counters mental fatigue
Cutsem, J. V., Pauw, K. D., Marcora, S., MEEUSEN, R. R., & Roelands, B. (2017) · Psychopharmacology · doi:10.1007/s00213-017-4809-0 · Cited by 97 · see citing works
Sip size of orangeade: effects on intake and sensory-specific satiation
Weijzen, P. L. G., Smeets, P. A. M., & de Graaf, C. (2009) · British Journal Of Nutrition · doi:10.1017/s000711450932574x · Cited by 95 · see citing works
Hormonal responses to non-nutritive sweeteners in water and diet soda
Sylvetsky, A. C., Brown, R. J., Blau, J. E., Walter, M. F., & Rother, K. I. (2016) · Nutrition & Metabolism · doi:10.1186/s12986-016-0129-3 · Cited by 94 · see citing works
“Furthermore, NNS have been shown to induce less central reward compared to caloric sugars [14], potentially leading to * Correspondence: kristina.”
Background
Gastrointestinal Interoception in Eating Disorders: Charting a New Path
Khalsa, S. S., Berner, L. A., & Anderson, L. M. (2022) · Current Psychiatry Reports · doi:10.1007/s11920-022-01318-3 · Cited by 100 · see citing works
“Other approaches have involved delivery of small amounts of tastants directly onto the tongue, such as sucrose solution [70], or milkshakes [71].”
Expected taste intensity affects response to sweet drinks in primary taste cortex
Woods, A. T., Lloyd, D. M., Kuenzel, J., Poliakoff, E., Dijksterhuis, G., & Thomas, A. K. (2011) · Neuroreport · doi:10.1097/wnr.0b013e3283469581 · Cited by 89 · see citing works
Food additives, food and the concept of ‘food addiction’: Is stimulation of the brain reward circuit by food sufficient to trigger addiction?
Onaolapo, A. Y., & Onaolapo, O. J. (2018) · Pathophysiology · doi:10.1016/j.pathophys.2018.04.002 · Cited by 91 · see citing works
The Role of Sweet Taste in Satiation and Satiety
Low, J. Y. Q., Lacy, K. E., & Keast, R. (2014) · Nutrients · doi:10.3390/nu6093431 · Cited by 84 · see citing works
“[75], researchers found that both caloric sugar and HIS were able to activate the primary taste pathway in the brain, but only caloric sugars were able to activate a significant response from brain regions involved in the brain’s reward pathway.”
Background
Dopamine and the interdependency of time perception and reward
Fung, B. J., Sutlief, E., & Shuler, M. G. H. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.02.030 · Cited by 79 · see citing works
Low Calorie Sweeteners Differ in Their Physiological Effects in Humans
Hunter, S., Reister, E. J., Cheon, E., & Mattes, R. D. (2019) · Nutrients · doi:10.3390/nu11112717 · Cited by 80 · see citing works
“Specifically, sucrose elicits greater dopamine release than saccharin in the nucleus accumbens core [112] and greater activation than sucralose in the anterior insula, frontal operculum, striatum and anterior cingulate [111].”
BackgroundInfluential
Current status of functional imaging in eating disorders
Frank, G., & Kaye, W. H. (2012) · International Journal of Eating Disorders · doi:10.1002/eat.22016 · Cited by 78 · see citing works
Self-citation
Taste uncoupled from nutrition fails to sustain the reinforcing properties of food
Beeler, J. A., McCutcheon, J. E., Cao, Z. F. H., Murakami, M., Alexander, E. R., Roitman, M. F., & Zhuang, X. (2012) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2012.08167.x · Cited by 73 · see citing works
“However, much of the data supporting the importance of hedonic value also arise from rodent work (but see Frank et al., 2008; Hursh & Silberberg, 2008; Haase et al., 2009).”
BackgroundResult
Characterizing consumer emotional response to sweeteners using an emotion terminology questionnaire and facial expression analysis
Leitch, K. A., Duncan, S. E., O’Keefe, S. F., Rudd, R. D., & Gallagher, D. L. (2015) · Food Research International · doi:10.1016/j.foodres.2015.04.039 · Cited by 74 · see citing works
EEG discrimination of perceptually similar tastes
Andersen, C. A., Kring, M. L., Andersen, R. H., Larsen, O. N., Kjær, T. W., Kidmose, U., Møller, S., & Kidmose, P. (2018) · Journal of Neuroscience Research · doi:10.1002/jnr.24281 · Cited by 69 · see citing works
Neuroendocrine and Metabolic Effects of Low-Calorie and Non-Calorie Sweeteners
Moriconi, E., Feraco, A., Marzolla, V., Infante, M., Lombardo, M., Fabbri, A., & Caprio, M. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00444 · Cited by 69 · see citing works
“Several brain regions are involved in food-reward, namely: lateral hypothalamic area (LHA), ventral tegmental area (VTA), nucleus accumbens (NAc) and prefrontal cortex (PFC).”
BackgroundInfluential
Sensing Via Intestinal Sweet Taste Pathways
Young, R. L. (2011) · Frontiers in Neuroscience · doi:10.3389/fnins.2011.00023 · Cited by 68 · see citing works
“In this respect sucralose is known to bind lingual sweet taste receptors with different affinity from sucrose, and shows differences in central activation in functional brain imaging (Nie et al., 2005; Frank et al., 2008).”
Background
The gut–brain axis in health neuroscience: implications for functional gastrointestinal disorders and appetite regulation
Weltens, N., Iven, J., Oudenhove, L. V., & Kano, M. (2018) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13969 · Cited by 67 · see citing works
Sweet Taste Is Complex: Signaling Cascades and Circuits Involved in Sweet Sensation
von Molitor, E., Riedel, K., Krohn, M., Hafner, M., Rudolf, R., & Cesetti, T. (2021) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2021.667709 · Cited by 58 · see citing works
Glucose elicits cephalic-phase insulin release in mice by activating KATP channels in taste cells.
Glendinning, J., Frim, Y. G., Hochman, A., Lubitz, G. S., Basile, A., & Sclafani, A. (2017) · American Journal of Physiology. Regulatory Integrative and Comparative Physiology · doi:10.1152/ajpregu.00433.2016 · Cited by 66 · see citing works
“Several studies have postulated the existence of a T1r2 T1r3-independent signaling pathway for tasting carbohydrates (16, 45, 62, 72), but this study is the first to implicate a specific pathway; namely, the KATP signaling pathway.”
Background
Relative sweetness and sensory characteristics of bulk and intense sweeteners
Gwak, M., Chung, S., Kim, Y., & Lim, C. S. (2012) · Food Science and Biotechnology · doi:10.1007/s10068-012-0115-0 · Cited by 65 · see citing works
“In the rating method, intensity of specific sensory attribute is measured using an interval scale (14-19).”
BackgroundMethod
Association of Body Mass and Brain Activation during Gastric Distention: Implications for Obesity
Tomasi, D., Wang, G.-J., Wang, R., Backus, W., Geliebter, A., Telang, F., Jayne, M. C., Wong, C., Fowler, J. S., & Volkow, N. D. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006847 · Cited by 64 · see citing works
“[53,54], food stimulation [55] and somatic and visceral-sensory processing (reviewed in [68]).”
Background
The neural signature of satiation is associated with ghrelin response and triglyceride metabolism
Sun, X., Veldhuizen, M. G., Wray, A. E., de Araújo, I. E., Sherwin, R. S., Sinha, R., & Small, D. M. (2014) · Physiology & Behavior · doi:10.1016/j.physbeh.2014.04.017 · Cited by 63 · see citing works
“Midbrain response has been shown to correlatewith subjective pleasantness ratings of chocolate [10] and sucrose [67], as well as to predict behavioral preference for food [68].”
Background
Sweetener aspartame aggravates atherosclerosis through insulin-triggered inflammation
Wu, W., Sui, W., Chen, S., Guo, Z., Jing, X., Wang, X., Wang, Q., Yu, X., Xiong, W., Ji, J., et al. (2025) · Cell Metabolism · doi:10.1016/j.cmet.2025.01.006 · Cited by 63 · see citing works
Intense Sweeteners, Appetite for the Sweet Taste, and Relationship to Weight Management
Bellisle, F. (2015) · Current Obesity Reports · doi:10.1007/s13679-014-0133-8 · Cited by 63 · see citing works
A head-to-head comparison review of biological and toxicological studies of isomaltulose, d -tagatose, and trehalose on glycemic control
Sokołowska, E., Sadowska, A. J., Sawicka, D., Kotulska-Bąblińska, I., & Car, H. (2021) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2021.1895057 · Cited by 61 · see citing works
“Frank et al. (2008) showed that sucrose, but not sucralose, engages dopaminergic midbrain areas concerning the behavioral response to pleasure.”
Background
Functional specialization of the male insula during taste perception
Dalenberg, J. R., Hoogeveen, H. R., Renken, R. J., Langers, D. R. M., & Horst, G. J. T. (2015) · NeuroImage · doi:10.1016/j.neuroimage.2015.06.062 · Cited by 60 · see citing works
“…many studies have focused on the (orbital) frontal cortex regarding pleasantness (liking or valence) responses, several studies have indeed suggested an association between gustatory valence responses and left insula activity (Bender et al., 2009; Cerf-Ducastel et al., 2012; Frank et al., 2008).”
Insights into brain perceptions of the different taste qualities and hedonic valence of food via scalp electroencephalogram
Yang, T., Zhang, P., Xing, L., Hu, J., Feng, R., Zhong, J., Li, W., Zhang, Y., Zhu, Q., Yang, Y., et al. (2023) · Food Research International · doi:10.1016/j.foodres.2023.113311 · Cited by 59 · see citing works
Self-citation
Can taste be ergogenic?
Best, R., McDonald, K., Hurst, P., & Pickering, C. (2020) · European Journal of Nutrition · doi:10.1007/s00394-020-02274-5 · Cited by 60 · see citing works
Intravascular Food Reward
Oliveira-Maia, A. J., Roberts, C. D., Walker, Q. D., Luo, B., Kuhn, C. M., Simon, S. A., & Nicolelis, M. A. L. (2011) · PLoS ONE · doi:10.1371/journal.pone.0024992 · Cited by 58 · see citing works
“latter activated dopaminergic midbrain areas [3].”
Psychophysical Evaluation of Sweetness Functions Across Multiple Sweeteners
Low, J. Y. Q., McBride, R., Lacy, K. E., & Keast, R. (2016) · Chemical Senses · doi:10.1093/chemse/bjw109 · Cited by 58 · see citing works
“data comparing NNS and caloric sweeteners in brain studies (Frank et al. 2008; Smeets et al. 2011; Green and Murphy 2012).”
Background
A rational review on the effects of sweeteners and sweetness enhancers on appetite, food reward and metabolic/adiposity outcomes in adults
O'Connor, D., Pang, M. D., Castelnuovo, G., Finlayson, G., Blaak, E. E., Gibbons, C., Navas‐Carretero, S., Almiron‐Roig, E., Harrold, J. A., Raben, A., et al. (2020) · Food & Function · doi:10.1039/d0fo02424d · Cited by 59 · see citing works
Similarities in hypothalamic and mesocorticolimbic circuits regulating the overconsumption of food and alcohol
Barson, J. R., Morganstern, I., & LEIBOWITZ, S. F. (2011) · Physiology & Behavior · doi:10.1016/j.physbeh.2011.04.054 · Cited by 56 · see citing works
The sweet taste signalling pathways in the oral cavity and the gastrointestinal tract affect human appetite and food intake: a review
Han, P., Bagenna, B., & Fu, M. (2018) · International Journal of Food Sciences and Nutrition · doi:10.1080/09637486.2018.1492522 · Cited by 55 · see citing works
“…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) !”
BackgroundInfluential
Involvement 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 · see citing works
Effects of the Daily Consumption of Stevia on Glucose Homeostasis, Body Weight, and Energy Intake: A Randomised Open-Label 12-Week Trial in Healthy Adults
Stamataki, N. S., Crooks, B. J., Ahmed, A., & McLaughlin, J. T. (2020) · Nutrients · doi:10.3390/nu12103049 · Cited by 53 · see citing works
“However, during NNS tasting the reward centres remained unresponsive [51,52].”
Background
BMI 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 53 · see citing works
“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].”
Background
Soft drinks and sweeteners intake: Possible contribution to the development of metabolic syndrome and cardiovascular diseases. Beneficial or detrimental action of alternative sweeteners?
Schiano, 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 54 · see citing works
The interrelationship of body mass index with gray matter volume and resting-state functional connectivity of the hypothalamus
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 · see citing works
Effect of Replacing Sugar with Non-Caloric Sweeteners in Beverages on the Reward Value after Repeated Exposure
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 · see citing works
“Several fMRI studies have shown that the brain can differentiate between sugar and sweeteners in several reward areas [9,10].”
BackgroundMethod
Oral Carbohydrate Rinse
Jeukendrup, A. E. (2013) · Current Sports Medicine Reports · doi:10.1249/jsr.0b013e31829a6caa · Cited by 45 · see citing works
“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.”
Background
Hunger 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 46 · see citing works
Obesity and Sex-Related Associations With Differential Effects of Sucralose vs Sucrose on Appetite and Reward Processing
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 · see citing works
A Systematic Review and Activation Likelihood Estimation Meta-Analysis of fMRI Studies on Sweet Taste in Humans
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 · see citing works
“0202 1336 Frontal operculum R 4 (16, 30, 31, 44) 26.”
Background
Carbonated soft drinks induce oxidative stress and alter the expression of certain genes in the brains of Wistar rats
El-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 · see citing works
Mouth Rinsing With Carbohydrate Solutions at the Postprandial State Fail to Improve Performance During Simulated Cycling Time Trials
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 41 · see citing works
“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).”
Background
Non-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 43 · see citing works
Recent studies of the effects of sugars on brain systems involved in energy balance and reward: Relevance to low calorie sweeteners
Murray, S. M., Tulloch, A. J., Criscitelli, K., & Avena, N. M. (2016) · Physiology & Behavior · doi:10.1016/j.physbeh.2016.04.004 · Cited by 41 · see citing works
“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 · see citing works
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 · see citing works
Effects of Non-nutritive Sweeteners on Sweet Taste Processing and Neuroendocrine Regulation of Eating Behavior
Yunker, A. G., Patel, R., & Page, K. A. (2020) · Current Nutrition Reports · doi:10.1007/s13668-020-00323-3 · Cited by 38 · see citing works
Sucralose and Cardiometabolic Health: Current Understanding from Receptors to Clinical Investigations
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 39 · see citing works
“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).”
Result
The Effects of Non-Nutritive Sweetener Consumption in the Pediatric Populations: What We Know, What We Don’t, and What We Need to Learn
Shum, B. J., & Georgia, S. K. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.625415 · Cited by 37 · see citing works
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 35 · see citing works
CARBOHYDRATE MOUTH RINSE: PERFORMANCE EFFECTS AND MECHANISMS
Jeukendrup, A. E., Rollo, I., & Carter, J. M. (2013) · Cited by 35 · see citing works
The Impact of Caloric and Non-Caloric Sweeteners on Food Intake and Brain Responses to Food: A Randomized Crossover Controlled Trial in Healthy Humans
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 36 · see citing works
“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].”
Background
Maltodextrin-Based Carbohydrate Oral Rinsing and Exercise Performance: Systematic Review and Meta-Analysis
Hartley, 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 · see citing works
“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.”
Background
Sucralose: From Sweet Success to Metabolic Controversies—Unraveling the Global Health Implications of a Pervasive Non-Caloric Artificial Sweetener
Aguayo-Guerrero, J. A., Méndez-García, L. A., Solleiro-Villavicencio, H., Viurcos-Sanabria, R., & Escobedo, G. (2024) · Life · doi:10.3390/life14030323 · Cited by 34 · see citing works
“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].”
Background
Dopamine D2 Receptor Genotype (C957T) and Habitual Consumption of Sugars in a Free-Living Population of Men and Women
Eny, K. M., Corey, P., & El‐Sohemy, A. (2009) · Lifestyle Genomics · doi:10.1159/000276991 · Cited by 34 · see citing works
“Sugars such as sucrose given orally and glucose infused intravenously stimulate dopaminergic regions of the brain [”
Background
Noncaloric 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 · see citing works
“The consumption of sugary beverages shows a positive effect on adiposity [39].”
Background
Dietary fat induces sustained reward response in the human brain without primary taste cortex discrimination
Tzieropoulos, H., Rytz, A., Hudry, J., & le Coutre, J. (2013) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2013.00036 · Cited by 34 · see citing works
“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).”
Result
The 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 · see citing works
“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).”
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De 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 30 · see citing works
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“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].”
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“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).”
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“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.”
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Non-caloric sweetener effects on brain appetite regulation in individuals across varying body weights
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Difference in human brain activation between caloric sucrose and an artificial sweetener
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Neural responses to oral administration of erythritol vs. sucrose and sucralose explain differences in subjective liking ratings
Budzinska, A., Teysseire, F., Flad, E., Dupont, P. J., Wölnerhanssen, B. K., Meyer‐Gerspach, A. C., Oudenhove, L. V., & Weltens, N. (2024) · Appetite · doi:10.1016/j.appet.2024.107422 · Cited by 9 · see citing works

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.
ORCID: Frank, Guido K.W.
Simmons, Alan N.
Paulus, Martin P.
Fudge, Julie L.
Yang, Tony T.
Kaye, Walter H.
Venue: NeuroImage
Publisher: Elsevier BV
Published: 2008-02
Volume: 39
Issue: 4
Pages: 1559-1569
ISSN: 1053-8119 (ISSN-L)
DOI: 10.1016/j.neuroimage.2007.10.061
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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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Sucrose activates human taste pathways differently from artificial sweetener

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