Effect of sucralose and aspartame on glucose metabolism and gut hormones

Nutrition Reviews

Volumn 78, Issue 9, 2020, Pages 725-746

  Ahmad, Samar Y ^a   Friel, James K ^a   MacKay, Dylan S ^b  

^a UNIVERSITY OF MANITOBA   (Canada)

^b UNIVERSITY OF MANITOBA   (Canada)

Author keywords

Aspartame; Glucose metabolism; Low calorie sweeteners; Non nutritive sweeteners; Sucralose

Indexed keywords

ACESULFAME; ASPARTAME; GASTROINTESTINAL HORMONE; GLUCAGON LIKE PEPTIDE 1; GLUCOSE; INSULIN; NEOTAME; NONNUTRITIVE SWEETENER; SACCHARIN; STEVIOL; SUCRALOSE; SUCROSE; TRICHLOROSUCROSE;

ADOLESCENT; ADULT; ARTICLE; CALORIC INTAKE; CARBOHYDRATE INTAKE; FEMALE; GLUCOSE BLOOD LEVEL; GLUCOSE METABOLISM; GLYCEMIC CONTROL; HUMAN; INSULIN BLOOD LEVEL; INSULIN SENSITIVITY; INTESTINE FLORA; MALE; RANDOMIZED CONTROLLED TRIAL (TOPIC); SIRAITIA GROSVENORII; TASTE BUD; ANIMAL; METABOLISM;

ANIMALS; ASPARTAME; GLUCAGON-LIKE PEPTIDE 1; GLUCOSE; HUMANS; INSULIN; NON-NUTRITIVE SWEETENERS; RANDOMIZED CONTROLLED TRIALS AS TOPIC; SUCROSE;

EID: 85089359091     PISSN: 00296643     EISSN: 17534887     Source Type: Journal    
DOI: 10.1093/nutrit/nuz099     Document Type: Article

References (96)

1. Johnson RK, Appel LJ, Brands M. Dietary sugars intake and cardiovascular health: a scientific statement from the American Heart Association. Circulation. 2009;120:1011-1020.
2. Malik VS, Popkin BM, Bray GA, et al. Sugar-sweetened beverages and risk of metabolic syndrome and type 2 diabetes: a meta-analysis. Diabetes Care. 2010;33:2477-2483.
3. Te Morenga L, Mallard S, Mann J. Dietary sugars and body weight: systematic review and meta-analyses of randomised controlled trials and cohort studies. BMJ. 2012;346:e7492.
4. Gardner C, Wylie-Rosett J, Gidding SS, et al. Nonnutritive sweeteners: current use and health perspectives: a scientific statement from the American Heart Association and the American Diabetes Association. Diabetes Care. 2012;35:1798-1808.
5. Mattes RD, Popkin BM. Nonnutritive sweetener consumption in humans: effects on appetite and food intake and their putative mechanisms. Am J Clin Nutr. 2009;89:1-14.
6. Malek AM, Hunt KJ, DellaValle DM, et al. Reported consumption of low-calorie sweetener in foods, beverages, and food and beverage additions by US adults: NHANES 2007-2012. Curr Dev Nutr. 2018;2:nzy054.doi:10.1093/cdn/nzy054
7. Sylvetsky AC, Jin Y, Clark EJ, et al. Consumption of low-calorie sweeteners among children and adults in the United States. J Acad Nutr Diet. 2017;117:441.e2-448.e2.
8. Drewnowski A, Rehm CD. Socio-demographic correlates and trends in low-calorie sweetener use among adults in the United States from 1999 to 2008. Eur J Clin Nutr. 2015;69:1035-1041.
9. Yang Q. Gain weight by "going diet?" Artificial sweeteners and the neurobiology of sugar cravings: Neuroscience 2010. Yale J Biol Med. 2010;83:101-108. PMID: 20589192
10. Peters JC, Beck J, Cardel M, et al. The effects of water and non-nutritive sweetened beverages on weight loss and weight maintenance: a randomized clinical trial. Obesity (Silver Spring). 2016;24:297-304.
11. Raben A, Richelsen B. Artificial sweeteners: a place in the field of functional foods? Focus on obesity and related metabolic disorders. Curr Opin Clin Nutr Metab Care. 2012;15:597-604.
12. Romo-Romo A, Aguilar-Salinas CA, Brito-Cordova GX, et al. Effects of the nonnutritive sweeteners on glucose metabolism and appetite regulating hormones: systematic review of observational prospective studies and clinical trials. PLoS One. 2016;11:e0161264.
13. Pepino MY, Bourne C. Non-nutritive sweeteners, energy balance, and glucose homeostasis. Curr Opin Clin Nutr Metab Care. 2011;14:391-395.
14. Brown RJ, de Banate MA, Rother KI. Artificial sweeteners: a systematic review of metabolic effects in youth. Int J Pediatr Obes. 2010;5:305-312.
15. Wiebe N, Padwal R, Field C, et al. A systematic review on the effect of sweeteners on glycemic response and clinically relevant outcomes. BMC Med. 2011;9:123.
16. US Food & Drug Administration. Additional information about high-intensity sweeteners permitted for use in food in the United States. https://www.fda.gov/ food/ingredientspackaginglabeling/foodadditivesingredients/ucm397725. htm#Luo_Han_Guo_fruit_extracts. Updated February 8, 2018. Accessed April 2, 2019.
17. Health Canada. List of permitted dweeteners (lists of permitted food additives). https://www.canada.ca/en/health-canada/services/food-nutrition/food-safety/ food-additives/lists-permitted/9-sweeteners.html. Updated June 27, 2019. Accessed April 4, 2019.
18. Sylvetsky AC, Rother KI. Trends in the consumption of low-calorie sweeteners. Physiol Behav. 2016;164:446-450.
19. George V, Arora S, Wadhwa BK, et al. Analysis of multiple sweeteners and their degradation products in lassi by HPLC and HPTLC plates. J Food Sci Technol. 2010;47:408-413.
20. Fitch C, Keim KS, for the Academy of Nutrition and Dietetics. Position of the Academy of Nutrition and Dietetics: use of nutritive and nonnutritive sweeteners [published correction appears in J Acad Nutr Diet. 2012;112:1279]. J Acad Nutr Diet. 2012;112:739-758.
21. Palmnas MSA, Cowan TE, Bomhof RM, et al. Low-dose aspartame consumption differentially affects gut microbiota-host metabolic interactions in the dietinduced obese rat. PLoS One. 2014;9:e109841.
22. Rowe RC, Sheskey PJ, Quinn ME. Handbook of Pharmaceutical Excipients. 6th ed. London, UK: Pharmaceutical Press; 2009.
23. Joint FAO/WHO Codex Alimentarius Commission. Codex Alimentarius: guidelines for the simple evaluation of dietary exposure to food additives. CAC/GL 3-1989. Geneva, Switzerland: World Health Organization; 2014.
24. US Food and Drug Administration, Department of Health and Human Services. Food labeling: health claims; dietary noncariogenic carbohydrate sweeteners and dental caries. Final rule. Fed Regist. 2006;71:15559-15564.
25. Knight I. The development and applications of sucralose, a new high-intensity sweetener. Can J Physiol Pharmacol. 1994;72:435-439.
26. Bornemann V, Werness SC, Buslinger L, et al. Intestinal metabolism and bioaccumulation of sucralose in adipose tissue in the rat. J Toxicol Environ Health A. 2018;81:913-923.
27. Abou-Donia MB, El-Masry EM, Abdel-Rahman AA, et al. Splenda alters gut microflora and increases intestinal p-glycoprotein and cytochrome p-450 in male rats. J Toxicol Environ Health A. 2008;71:1415-1429.
28. Nelson G, Hoon MA, Chandrashekar J, et al. Mammalian sweet taste receptors. Cell. 2001;106:381-390.
29. Chandrashekar J, Hoon MA, Ryba NJ, et al. The receptors and cells for mammalian taste. Nature. 2006;444:288-294.
30. Fernstrom JD, Munger SD, Sclafani A, et al. Mechanisms for sweetness. J Nutr. 2012;142:1134S-1141S.
31. Nakagawa Y, Nagasawa M, Yamada S, et al. Sweet taste receptor expressed in pancreatic b-cells activates the calcium and cyclic AMP signaling systems and stimulates insulin secretion. PLoS One. 2009;4:e5106.
32. Kojima I, Nakagawa Y. The role of the sweet taste receptor in enteroendocrine cells and pancreatic b-cells. Diabetes Metab J. 2011;35:451-457.
33. Chen L, Tuo B, Dong H. Regulation of intestinal glucose absorption by ion channels and transporters. Nutrients. 2016;8:43.
34. Kim HR, Park SW, Cho HJ, et al. Comparative gene expression profiles of intestinal transporters in mice, rats and humans. Pharmacol Res. 2007;56:224-236.
35. Nauck MA, Meier JJ. Incretin hormones: their role in health and disease. Diabetes Obes Metab. 2018;20(suppl 1):5-21.
36. Jang HJ, Kokrashvili Z, Theodorakis MJ, et al. Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1. Proc Natl Acad Sci USA. 2007;104:15069-15074.
37. Margolskee RF, Dyer J, Kokrashvili Z, et al. T1R3 and gustducin in gut sense sugars to regulate expression of Nap-glucose cotransporter 1. Proc Natl Acad Sci USA. 2007;104:15075-15080.
38. Mace OJ, Affleck J, Patel N, et al. Sweet taste receptors in rat small intestine stimulate glucose absorption through apical GLUT2. J Physiol. 2007;582(pt 2):379-392.
39. Saada HN, Mekky NH, Eldawy HA, et al. Biological effect of sucralose in diabetic rats. Food Nutr Sci. 2013;4:82-89.
40. Fujita Y, Wideman RD, Speck M, et al. Incretin release from gut is acutely enhanced by sugar but not by sweeteners in vivo. Am J Physiol Endocrinol Metab. 2009;296:E473-E479.
41. Brown RJ, Walter M, Rother KI. Effects of diet soda on gut hormones in youths with diabetes. Diabetes Care. 2012;35:959-964.
42. Lertrit A, Srimachai S, Saetung S, et al. Effects of sucralose on insulin and glucagon-like peptide-1 secretion in healthy subjects: a randomized, doubleblind, placebo-controlled trial. Nutrition. 2018;55-56:125-130.
43. Hall WL, Millward DJ, Rogers PJ, et al. Physiological mechanisms mediating aspartame-induced satiety. Physiol Behav. 2003;78:557-562.
44. Pepino MY, Tiemann CD, Patterson BW, et al. Sucralose affects glycemic and hormonal responses to an oral glucose load. Diabetes Care. 2013;36:2530-2535.
45. Moller SE. Effect of aspartame and protein, administered in phenylalanineequivalent doses, on plasma neutral amino acids, aspartate, insulin and glucose in man. Pharmacol Toxicol. 1991;68:408-412. doi:10.1111/j.1600-0773.1991.tb01262.x
46. Melanson KJ, Westerterp-Plantenga MS, Campfield LA, et al. Blood glucose and meal patterns in time-blinded males, after aspartame, carbohydrate, and fat consumption, in relation to sweetness perception. Br J Nutr. 1999;82:437-446.
47. Mezitis NH, Maggio CA, Koch P, et al. Glycemic effect of a single high oral dose of the novel sweetener sucralose in patients with diabetes. Diabetes Care. 1996;19:1004-1005.
48. Baird IM, Shephard NW, Merritt RJ, et al. Repeated dose study of sucralose tolerance in human subjects. Food Chem Toxicol. 2000;38(suppl 2):S123-S129.
49. Grotz VL, Henry RR, McGill JB, et al. Lack of effect of sucralose on glucose homeostasis in subjects with type 2 diabetes. J Am Diet Assoc. 2003;103:1607-1612.
50. Reyna NY, Cano C, Bermúdez VJ, et al. Sweeteners and beta-glucans improve metabolic and anthropometrics variables in well controlled type 2 diabetic patients. Am J Ther. 2003;10:438-443.
51. Ma J, Bellon M, Wishart JM, et al. Effect of the artificial sweetener, sucralose, on gastric emptying and incretin hormone release in healthy subjects. Am J Physiol Gastrointest Liver Physiol. 2009;296:G735-G739. Brown RJ, Walter M, Rother KI. Ingestion of diet soda before a glucose load augments glucagon-like peptide-1 secretion. Diabetes Care. 2009;32:2184-2186.
52. Ma J, Chang J, Checklin HL, et al. Effect of the artificial sweetener, sucralose, on small intestinal glucose absorption in healthy human subjects. Br J Nutr. 2010;104:803-806.
53. Brown AW, Bohan Brown MM, Onken KL, et al. Short-term consumption of sucralose, a nonnutritive sweetener, is similar to water with regard to select markers of hunger signaling and short-term glucose homeostasis in women. Nutr Res. 2011;31:882-888.
54. Steinert RE, Frey F, Topfer A, et al. Effects of carbohydrate sugars and artificial sweeteners on appetite and the secretion of gastrointestinal satiety peptides. Br J Nutr. 2011;105:1320-1328.
55. Ford HE, Peters V, Martin NM, et al. Effects of oral ingestion of sucralose on gut hormone response and appetite in healthy normal-weight subjects. Eur J Clin Nutr. 2011;65:508-513.
56. Wu T, Zhao BR, Bound MJ, et al. Effects of different sweet preloads on incretin hormone secretion, gastric emptying, and postprandial glycemia in healthy humans. Am J Clin Nutr. 2012;95:78-83.
57. Wu T, Bound MJ, Standfield SD, et al. Artificial sweeteners have no effect on gastric emptying, glucagon-like peptide-1, or glycemia after oral glucose in healthy humans. Diabetes Care. 2013;36:e202-e203.
58. Stellingwerff T, Godin JP, Beaumont M, et al. Effects of pre-exercise sucralose ingestion on carbohydrate oxidation during exercise. Int J Sport Nutr Exerc Metab. 2013;23:584-592.
59. Temizkan S, Deyneli O, Yasar M, et al. Sucralose enhances GLP-1 release and lowers blood glucose in the presence of carbohydrate in healthy subjects but not in patients with type 2 diabetes. Eur J Clin Nutr. 2015;69:162-166.
60. Sylvetsky AC, Brown RJ, Blau JE, et al. Hormonal responses to non-nutritive sweeteners in water and diet soda. Nutr Metab (Lond). 2016;13:71.
61. Grotz VL, Pi-Sunyer X, Porte D Jr, et al. A 12-week randomized clinical trial investigating the potential for sucralose to affect glucose homeostasis. Regul Toxicol Pharmacol. 2017;88:22-33.
62. Romo-Romo A, Aguilar-Salinas CA, Brito-Córdova GX, et al. Sucralose decreases insulin sensitivity in healthy subjects: a randomized controlled trial. Am J Clin Nutr. 2018;108:485-491.
63. Nehrling JK, Kobe P, McLane MP, et al. Aspartame use by persons with diabetes. Diabetes Care. 1985;8:415-417.
64. Horwitz DL, McLane M, Kobe P. Response to single dose of aspartame or saccharin by NIDDM patients. Diabetes Care. 1988;11:230-234.
65. Colagiuri S, Miller JJ, Edwards RA. Metabolic effects of adding sucrose and aspartame to the diet of subjects with noninsulin-dependent diabetes mellitus. Am J Clin Nutr. 1989;50:474-478.
66. Rodin J. Comparative effects of fructose, aspartame, glucose, and water preloads on calorie and macronutrient intake. Am J Clin Nutr. 1990;51:428-435.
67. Härtel B, Graubaum J-H, Schneider B. The influence of sweetener solutions on the secretion of insulin and the blood glucose level. Ernährungsumschau. 1993;40:152-155. http://www.aspartame.net/onpagepdf/the-influence-of-sweetener- solutions-on-the-secretion-of-insulin-and-the-blood-glucose-level.pdf
68. Anton SD, Martin CK, Han H, et al. Effects of stevia, aspartame, and sucrose on food intake, satiety, and postprandial glucose and insulin levels. Appetite. 2010;55:37-43.
69. Maersk M, Belza A, Holst JJ, et al. Satiety scores and satiety hormone response after sucrose-sweetened soft drink compared with isocaloric semi-skimmed milk and with non-caloric soft drink: a controlled trial. Eur J Clin Nutr. 2012;66:523-529.
70. Olalde-Mendoza L, Moreno-González YE. Modification of fasting blood glucose in adults with diabetes mellitus type 2 after regular soda and diet soda intake in the State of Queretaro, Mexico [in Spanish]. Arch Latinoam Nutr. 2013;63:142-147. PMID: 24934070
71. Bryant CE, Wasse LK, Astbury N, et al. Non-nutritive sweeteners: no class effect on the glycaemic or appetite responses to ingested glucose. Eur J Clin Nutr. 2014;68:629-631.
72. Tey SL, Salleh NB, Henry CJ, et al. Effects of non-nutritive (artificial vs natural) sweeteners on 24-h glucose profiles. Eur J Clin Nutr. 2017;71:1129-1132.
73. Higgins KA, Considine RV, Mattes RD. Aspartame consumption for 12 weeks does not affect glycemia, appetite, or body weight of healthy, lean adults in a randomized controlled trial. J Nutr. 2018;148:650-657.
74. Bonnet F, Tavenard A, Esvan M, et al. Consumption of a carbonated beverage with high-intensity sweeteners has no effect on insulin sensitivity and secretion in nondiabetic adults. J Nutr. 2018;148:1293-1299.
75. Berthoud HR, Bereiter DA, Trimble ER, et al. Cephalic phase, reflex insulin secretion. Neuroanatomical and physiological characterization. Diabetologia. 1981;20(suppl):393-401.
76. Powley TL, Berthoud HR. Diet and cephalic phase insulin responses. Am J Clin Nutr. 1985;42:991-1002.
77. Kraegen EW, Chisholm DJ, McNamara ME. Timing of insulin delivery with meals. Horm Metab Res. 1981;13:365-367.
78. Teff KL, Mattes RD, Engelman K, et al. Cephalic-phase insulin in obese and normalweightmen: relation to postprandial insulin. Metabolism. 1993;42:1600-1608.
79. Teff KL, Engelman K. Oral sensory stimulation improves glucose tolerance in humans: effects on insulin, C-peptide, and glucagon. Am J Physiol. 1996;270(6 pt 2):R1371-R1379.
80. Bellisle F, Louis-Sylvestre J, Demozay F, et al. Cephalic phase of insulin secretion and food stimulation in humans: a new perspective. Am J Physiol. 1985;249(6 pt 1):E639-E645.
81. Bernstein IL, Woods SC. Ontogeny of cephalic insulin release by the rat. Physiol Behav. 1980;24:529-532.
82. Ahren B, Holst JJ. The cephalic insulin response to meal ingestion in humans is dependent on both cholinergic and noncholinergic mechanisms and is important for postprandial glycemia. Diabetes. 2001;50:1030-1038.
83. Just T, Pau HW, Engel U, et al. Cephalic phase insulin release in healthy humans after taste stimulation? Appetite. 2008;51:622-627.
84. Ley RE, Peterson DA, Gordon JI. Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell. 2006;124:837-848.
85. Kunz C, Kuntz S, Rudloff S. Intestinal flora. Adv Exp Med Biol. 2009;639:67-79.
86. Ferreiro A, Crook N, Gasparrini AJ, et al. Multiscale evolutionary dynamics of hostassociated microbiomes. Cell. 2018;172:1216-1227.
87. Eckburg PB, Bik EM, Bernstein CN, et al. Diversity of the human intestinal microbial flora. Science. 2005;308:1635-1638.
88. Jandhyala SM, Talukdar R, Subramanyam C, et al. Role of the normal gut microbiota. World J Gastroenterol. 2015;21:8787-8803.
89. Pickard JM, Zeng MY, Caruso R, et al. Gut microbiota: role in pathogen colonization, immune responses, and inflammatory disease. Immunol Rev. 2017;279:70-89.
90. Hooks KB, O'Malley MA. Dysbiosis and its discontents. MBio. 2017;8:e01492-17.
91. Martinez KB, Leone V, Chang EB. Western diets, gut dysbiosis, and metabolic diseases: are they linked? Gut Microbes. 2017;8:130-142.
92. Suez J, Korem T, Zeevi D, et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature. 2014;514:181-186.
93. Myles IA. Fast food fever: reviewing the impacts of the Western diet on immunity. Nutr J. 2014;13:61.
94. Swithers SE. Artificial sweeteners produce the counterintuitive effect of inducing metabolic derangements. Trends Endocrinol Metab. 2013;24:431-441.
95. Walters WA, Knight R. Technology and techniques for microbial ecology via DNA sequencing. Ann Am Thorac Soc. 2014;11(suppl 1):S16-S20.
96. Zeevi D, Korem T, Zmora N, et al. Personalized nutrition by prediction of glycemic responses. Cell. 2015;163:1079-1094.