Skip to main content

Thank you for visiting 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.

Effects of oral ingestion of sucralose on gut hormone response and appetite in healthy normal-weight subjects



The sweet-taste receptor (T1r2+T1r3) is expressed by enteroendocrine L-cells throughout the gastrointestinal tract. Application of sucralose (a non-calorific, non-metabolisable sweetener) to L-cells in vitro stimulates glucagon-like peptide (GLP)-1 secretion, an effect that is inhibited with co-administration of a T1r2+T1r3 inhibitor. We conducted a randomised, single-blinded, crossover study in eight healthy subjects to investigate whether oral ingestion of sucralose could stimulate L-cell-derived GLP-1 and peptide YY (PYY) release in vivo.


Fasted subjects were studied on 4 study days in random order. Subjects consumed 50 ml of either water, sucralose (0.083% w/v), a non-sweet, glucose-polymer matched for sweetness with sucralose addition (50% w/v maltodextrin+0.083% sucralose) or a modified sham-feeding protocol (MSF=oral stimulation) of sucralose (0.083% w/v). Appetite ratings and plasma GLP-1, PYY, insulin and glucose were measured at regular time points for 120 min. At 120 min, energy intake at a buffet meal was measured.


Sucralose ingestion did not increase plasma GLP-1 or PYY. MSF of sucralose did not elicit a cephalic phase response for insulin or GLP-1. Maltodextrin ingestion significantly increased insulin and glucose compared with water (P<0.001). Appetite ratings and energy intake were similar for all groups.


At this dose, oral ingestion of sucralose does not increase plasma GLP-1 or PYY concentrations and hence, does not reduce appetite in healthy subjects. Oral stimulation with sucralose had no effect on GLP-1, insulin or appetite.

Your institute does not have access to this article

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1


  • Abdallah L, Chabert M, Louis-Sylvestre J (1997). Cephalic phase responses to sweet taste. Am J Clin Nutr 65, 737–743.

    CAS  Article  Google Scholar 

  • Adrian TE, Ferri GL, Bacarese-Hamilton AJ, Fuessl HS, Polak JM, Bloom SR (1985). Human distribution and release of a putative new gut hormone, peptide YY. Gastroenterology 89, 1070–1077.

    CAS  Article  Google Scholar 

  • Ahren B, Holst JJ (2001). The cephalic insulin response to meal ingestion in humans is dependent on both cholinergic and noncholinergic mechanisms and is important for postprandial glycemia. Diabetes 50, 1030–1038.

    CAS  Article  Google Scholar 

  • Batterham RL, Cowley MA, Small CJ, Herzog H, Cohen MA, Dakin CL et al. (2002). Gut hormone PYY(3-36) physiologically inhibits food intake. Nature 418, 650–654.

    CAS  Article  Google Scholar 

  • Bray GA, Nielsen SJ, Popkin BM (2004). Consumption of high-fructose corn syrup in beverages may play a role in the epidemic of obesity. Am J Clin Nutr 79, 537–543.

    CAS  Article  Google Scholar 

  • Brown RJ, Walter M, Rother KI (2009). Ingestion of diet soda before a glucose load augments GLP-1 secretion. Diabetes Care 32, 2184–2186.

    CAS  Article  Google Scholar 

  • Challis BG, Pinnock SB, Coll AP, Carter RN, Dickson SL, O’rahilly S (2003). Acute effects of PYY3-36 on food intake and hypothalamic neuropeptide expression in the mouse. Biochem Biophys Res Commun 311, 915–919.

    CAS  Article  Google Scholar 

  • Chelikani PK, Haver AC, Reeve Jr JR, Keire DA, Reidelberger RD (2006). Daily, intermittent intravenous infusion of peptide YY(3-36) reduces daily food intake and adiposity in rats. Am J Physiol Regul Integr Comp Physiol 290, R298–R305.

    CAS  Article  Google Scholar 

  • Chelikani PK, Haver AC, Reidelberger RD (2005a). Intravenous infusion of peptide YY(3-36) potently inhibits food intake in rats. Endocrinology 146, 879–888.

    CAS  Article  Google Scholar 

  • Chelikani PK, Haver AC, Reidelberger RD (2005b). Intravenous infusion of glucagon-like peptide-1 potently inhibits food intake, sham feeding, and gastric emptying in rats. Am J Physiol Regul Integr Comp Physiol 288, R1695–R1706.

    CAS  Article  Google Scholar 

  • Christofides ND, Sarson DL, Albuquerque RH, Adrian TE, Ghatei MA, Modlin IM et al. (1979). Release of gastrointestinal hormones following an oral water load. Experientia 35, 1521–1523.

    CAS  Article  Google Scholar 

  • Degen L, Oesch S, Casanova M, Graf S, Ketterer S, Drewe J et al. (2005). Effect of peptide YY3-36 on food intake in humans. Gastroenterology 129, 1430–1436.

    CAS  Article  Google Scholar 

  • Elliott SS, Keim NL, Stern JS, Teff K, Havel PJ (2002). Fructose, weight gain, and the insulin resistance syndrome. Am J Clin Nutr 76, 911–922.

    CAS  Article  Google Scholar 

  • Elrick H, Stimmler L, Hlad Jr CJ, Rai Y (1964). Plasma insulin response to oral and intravenous glucose administration. J Clin Endocrinol Metab 24, 1076–1082.

    CAS  Article  Google Scholar 

  • Flint A, Raben A, Astrup A, Holst JJ (1998). Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans. J Clin Invest 101, 515–520.

    CAS  Article  Google Scholar 

  • Flint A, Raben A, Blundell JE, Astrup A (2000). Reproducibility, power and validity of visual analogue scales in assessment of appetite sensations in single test meal studies. Int J Obes Relat Metab Disord 24, 38–48.

    CAS  Article  Google Scholar 

  • Fujita Y, Wideman RD, Speck M, Asadi A, King DS, Webber TD et al. (2009). Incretin release from gut is acutely enhanced by sugar but not by sweeteners in vivo. Am J Physiol Endocrinol Metab 296, E473–E479.

    CAS  Article  Google Scholar 

  • Ghatei MA, Uttenthal LO, Christofides ND, Bryant MG, Bloom SR (1983). Molecular forms of human enteroglucagon in tissue and plasma: plasma responses to nutrient stimuli in health and in disorders of the upper gastrointestinal tract. J Clin Endocrinol Metab 57, 488–495.

    CAS  Article  Google Scholar 

  • Grice HC, Goldsmith LA (2000). Sucralose—an overview of the toxicity data. Food Chem Toxicol 38 (Suppl 2), S1–S6.

    CAS  Article  Google Scholar 

  • Grotz VL, Henry RR, McGill JB, Prince MJ, Shamoon H, Trout JR et al. (2003). Lack of effect of sucralose on glucose homeostasis in subjects with type 2 diabetes. J Am Diet Assoc 103, 1607–1612.

    Article  Google Scholar 

  • Gutzwiller JP, Goke B, Drewe J, Hildebrand P, Ketterer S, Handschin D et al. (1999). Glucagon-like peptide-1: a potent regulator of food intake in humans. Gut 44, 81–86.

    CAS  Article  Google Scholar 

  • Halatchev IG, Ellacott KL, Fan W, Cone RD (2004). Peptide YY3-36 inhibits food intake in mice through a melanocortin-4 receptor-independent mechanism. Endocrinology 145, 2585–2590.

    CAS  Article  Google Scholar 

  • Hall WL, Millward DJ, Rogers PJ, Morgan LM (2003). Physiological mechanisms mediating aspartame-induced satiety. Physiol Behav 78, 557–562.

    CAS  Article  Google Scholar 

  • Jang HJ, Kokrashvili Z, Theodorakis MJ, Carlson OD, Kim BJ, Zhou J et al. (2007). Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1. Proc Natl Acad Sci USA 104, 15069–15074.

    CAS  Article  Google Scholar 

  • Kreymann B, Williams G, Ghatei MA, Bloom SR (1987). Glucagon-like peptide-1 7–36: a physiological incretin in man. Lancet 2, 1300–1304.

    CAS  Article  Google Scholar 

  • Le Roux CW, Batterham RL, Aylwin SJ, Patterson M, Borg CM, Wynne KJ et al. (2006). Attenuated peptide YY release in obese subjects is associated with reduced satiety. Endocrinology 147, 3–8.

    CAS  Article  Google Scholar 

  • Li X, Staszewski L, Xu H, Durick K, Zoller M, Adler E (2002). Human receptors for sweet and umami taste. Proc Natl Acad Sci USA 99, 4692–4696.

    CAS  Article  Google Scholar 

  • Luscombe-Marsh ND, Smeets AJ, Westerterp-Plantenga MS (2009). The addition of monosodium glutamate and inosine monophosphate-5 to high-protein meals: effects on satiety, and energy and macronutrient intakes. Br J Nutr 102, 929–937.

    CAS  Article  Google Scholar 

  • Ma J, Bellon M, Wishart JM, Young R, Blackshaw LA, Jones KL et al. (2009). Effect of the artificial sweetener, sucralose, on gastric emptying and incretin hormone release in healthy subjects. Am J Physiol Gastrointest Liver Physiol 296, G735–G739.

    CAS  Article  Google Scholar 

  • Morgan JF, Reid F, Lacey JH (2000). The SCOFF questionnaire: a new screening tool for eating disorders. West J Med 172, 164–165.

    CAS  Article  Google Scholar 

  • Murphy KG, Bloom SR (2006). Gut hormones and the regulation of energy homeostasis. Nature 444, 854–859.

    CAS  Article  Google Scholar 

  • Nelson G, Hoon MA, Chandrashekar J, Zhang Y, Ryba NJ, Zuker CS (2001). Mammalian sweet taste receptors. Cell 106, 381–390.

    CAS  Article  Google Scholar 

  • Parker HE, Reimann F, Gribble FM (2010). Molecular mechanisms underlying nutrient-stimulated incretin secretion. Expert Rev Mol Med 12, e1.

    Article  Google Scholar 

  • Raben A, Vasilaras TH, Moller AC, Astrup A (2002). Sucrose compared with artificial sweeteners: different effects on ad libitum food intake and body weight after 10 wk of supplementation in overweight subjects. Am J Clin Nutr 76, 721–729.

    CAS  Article  Google Scholar 

  • Reimann F, Habib AM, Tolhurst G, Parker HE, Rogers GJ, Gribble FM (2008). Glucose sensing in L cells: a primary cell study. Cell Metab 8, 532–539.

    CAS  Article  Google Scholar 

  • Rozengurt N, Wu SV, Chen MC, Huang C, Sternini C, Rozengurt E (2006). Colocalization of the alpha-subunit of gustducin with PYY and GLP-1 in L cells of human colon. Am J Physiol Gastrointest Liver Physiol 291, G792–G802.

    CAS  Article  Google Scholar 

  • Sutherland K, Young RL, Cooper NJ, Horowitz M, Blackshaw LA (2007). Phenotypic characterization of taste cells of the mouse small intestine. Am J Physiol Gastrointest Liver Physiol 292, G1420–G1428.

    CAS  Article  Google Scholar 

  • Talsania T, Anini Y, Siu S, Drucker DJ, Brubaker PL (2005). Peripheral exendin-4 and peptide YY(3-36) synergistically reduce food intake through different mechanisms in mice. Endocrinology 146, 3748–3756.

    CAS  Article  Google Scholar 

  • Teff KL, Devine J, Engelman K (1995). Sweet taste: effect on cephalic phase insulin release in men. Physiol Behav 57, 1089–1095.

    CAS  Article  Google Scholar 

  • Van Strien T, Rookus MA, Bergers GP, Frijters JE, Defares PB (1986). Life events, emotional eating and change in body mass index. Int J Obes 10, 29–35.

    CAS  PubMed  Google Scholar 

  • Wong GT, Gannon KS, Margolskee RF (1996). Transduction of bitter and sweet taste by gustducin. Nature 381, 796–800.

    CAS  Article  Google Scholar 

Download references


We thank Mandy Donaldson and John Meek for glucose and insulin assays, the Sir John McMichael research centre for Clinical Investigation and Research, Hammersmith Hospital and the volunteers. VP is funded through a European Union framework 6 Marie Curie fellowship (NuSISCO). NMM is funded by a HEFCE Clinical Senior Lecturer Award. This research is funded by program grants from the MRC (G7811974) and Wellcome Trust (072643/Z/03/Z) and by an EU FP6 Integrated Project Grant LSHM-CT-2003-503041. We are also grateful for support from the NIHR Biomedical Research Centre funding scheme. We thank Tate and Lyle for the provision of sucralose.

Author information

Authors and Affiliations


Corresponding author

Correspondence to S R Bloom.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Contributors: HEF and VP designed the experiment, collected and analysed data and wrote the manuscript. NMM helped with the writing of the manuscript. MS contributed to the data analysis. MAG, GSF and SRB provided significant advice.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Ford, H., Peters, V., Martin, N. et al. Effects of oral ingestion of sucralose on gut hormone response and appetite in healthy normal-weight subjects. Eur J Clin Nutr 65, 508–513 (2011).

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:


  • obesity
  • sucralose
  • sweetener
  • gut hormone
  • appetite

Further reading


Quick links