A randomized controlled trial contrasting the effects of 4 low-calorie sweeteners and sucrose on body weight in adults with overweight or obesity

American Journal of Clinical Nutrition

Volumn 109, Issue 5, 2019, Pages 1288-1301

  Higgins, Kelly A ^a   Mattes, Richard D ^b  

^a PURDUE UNIVERSITY   (United States)

^b PURDUE UNIVERSITY   (United States)

Author keywords

Appetite; Energy intake; Glycemia; Ingestive behavior; Low calorie sweeteners; Obesity; Overweight; Sweetness

Indexed keywords

4 AMINOBENZOIC ACID; ASPARTAME; BORIC ACID; GLUCOSE; HEMOGLOBIN A1C; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; INSULIN; LOW DENSITY LIPOPROTEIN CHOLESTEROL; REBAUDIOSIDE A; SACCHARIN; SUCRALOSE; SUCROSE; SWEETENING AGENT; TRIACYLGLYCEROL; UNCLASSIFIED DRUG; WATER; KAURANE DERIVATIVE; NONNUTRITIVE SWEETENER; TRICHLOROSUCROSE;

ADULT; ANTHROPOMETRY; APPETITE; ARTICLE; BODY MASS; BODY WEIGHT; BODY WEIGHT CHANGE; CALORIC INTAKE; CHOLESTEROL BLOOD LEVEL; CONTROLLED STUDY; DIETARY COMPLIANCE; ENERGY EXPENDITURE; FAT MASS; FEMALE; FOLLOW UP; GLUCOSE BLOOD LEVEL; HEMOGLOBIN BLOOD LEVEL; HUMAN; INSULIN BLOOD LEVEL; LOW CALORIE DIET; MAJOR CLINICAL STUDY; MALE; OBESITY; ORAL GLUCOSE TOLERANCE TEST; PARALLEL DESIGN; PORTION SIZE; RANDOMIZED CONTROLLED TRIAL; TOTAL BODY WATER; TRIACYLGLYCEROL BLOOD LEVEL; URINE SAMPLING; BEVERAGE; BODY WEIGHT GAIN; COMPARATIVE STUDY; DIET; DRUG EFFECT; FEEDING BEHAVIOR; METABOLISM; PHARMACOLOGY; STEVIA; SUGAR INTAKE; YOUNG ADULT;

ADULT; ASPARTAME; BEVERAGES; BODY MASS INDEX; BODY WEIGHT; DIET; DIETARY SUCROSE; DITERPENES, KAURANE; ENERGY INTAKE; FEEDING BEHAVIOR; FEMALE; HUMANS; MALE; NON-NUTRITIVE SWEETENERS; OBESITY; OVERWEIGHT; SACCHARIN; STEVIA; SUCROSE; SWEETENING AGENTS; WEIGHT GAIN; YOUNG ADULT;

EID: 85065598975     PISSN: 00029165     EISSN: 19383207     Source Type: Journal    
DOI: 10.1093/ajcn/nqy381     Document Type: Article

References (78)

1. Sylvetsky AC, Jin Y, Clark EJ, Welsh JA, Rother KI, Talegawkar SA. Consumption of low-calorie sweeteners among children and adults in the United States. J Acad Nutr Diet 2017;117(3):441-8 e2.
2. Rogers PJ, Hogenkamp PS, de Graaf C, Higgs S, Lluch A, Ness AR, Penfold C, Perry R, Putz P, Yeomans MR, et al. Does low-energy sweetener consumption affect energy intake and body weight? A systematic review, including meta-analyses, of the evidence from human and animal studies. Int J Obes (Lond) 2016;40(3):381-94.
3. Miller PE, Perez V. Low-calorie sweeteners and body weight and composition: a meta-analysis of randomized controlled trials and prospective cohort studies. Am J Clin Nutr 2014;100(3):765-77.
4. Azad MB, Abou-Setta AM, Chauhan BF, Rabbani R, Lys J, Copstein L, Mann A, Jeyaraman MM, Reid AE, Fiander M, et al. Nonnutritive sweeteners and cardiometabolic health: a systematic review and meta-analysis of randomized controlled trials and prospective cohort studies. CMAJ 2017;189(28):E929-E39.
5. Fowler SP, Williams K, Resendez RG, Hunt KJ, Hazuda HP, Stern MP. Fueling the obesity epidemic? Artificially sweetened beverage use and long-term weight gain. Obesity (Silver Spring) 2008;16(8):1894-900.
6. Egan JM, Margolskee RF. Taste cells of the gut and gastrointestinal chemosensation. Mol Interv 2008;8(2):78-81.
7. Swithers SE, Davidson TL. A role for sweet taste: calorie predictive relations in energy regulation by rats. Behav Neurosci 2008;122(1):161.
8. Nie Y, Vigues S, Hobbs JR, Conn GL, Munger SD. Distinct contributions of T1R2 and T1R3 taste receptor subunits to the detection of sweet stimuli. Curr Biol 2005;15(21):1948-52.
9. Masuda K, Koizumi A, Nakajima K-i, Tanaka T, Abe K, Misaka T, Ishiguro M. Characterization of the modes of binding between human sweet taste receptor and low-molecular-weight sweet compounds. PLoS One 2012;7(4):e35380.
10. Kim S-K, Chen Y, Abrol R, Goddard WA, Guthrie B. Activation mechanism of the G protein-coupled sweet receptor heterodimer with sweeteners and allosteric agonists. Proc Natl Acad Sci U S A 2017;114(10):2568-73.
11. Nakagawa Y, Nagasawa M, Mogami H, Lohse M, Ninomiya Y, Kojima I. Multimodal function of the sweet taste receptor expressed in pancreatic β-cells: generation of diverse patterns of intracellular signals by sweet agonists. Endocr J 2013;60(10):1191-206.
12. DuBois GE, Prakash I. Non-caloric sweeteners, sweetness modulators, and sweetener enhancers. Annu Rev Food Sci Technol 2012;3: 353-80.
13. Just T, Pau HW, Engel U, Hummel T. Cephalic phase insulin release in healthy humans after taste stimulation? Appetite 2008;51(3):622-7.
14. Dhillon J, Lee JY, Mattes RD. The cephalic phase insulin response to nutritive and low-calorie sweeteners in solid and beverage form. Physiol Behav 2017;181:100-9.
15. Ford HE, Peters V, Martin NM, Sleeth ML, Ghatei MA, Frost GS, Bloom SR. Effects of oral ingestion of sucralose on gut hormone response and appetite in healthy normal-weight subjects. Eur J Clin Nutr 2011;65(4):508-13.
16. Abdallah L, Chabert M, Louis-Sylvestre J. Cephalic phase responses to sweet taste. Am J Clin Nutr 1997;65(3):737-43.
17. Teff KL, Devine J, Engelman K. Sweet taste: effect on cephalic phase insulin release in men. Physiol Behav 1995;57(6):1089-95.
18. Smeets PA, Erkner A, De Graaf C. Cephalic phase responses and appetite. Nutr Rev 2010;68(11):643-55.
19. Swithers SE, Martin AA, Davidson TL. High-intensity sweeteners and energy balance. Physiol Behav 2010;100(1):55-62.
20. Steinert RE, Frey F, Töpfer A, Drewe J, Beglinger C. Effects of carbohydrate sugars and artificial sweeteners on appetite and the secretion of gastrointestinal satiety peptides. Br J Nutr 2011;105(9):1320-8.
21. Roberts A, Renwick AG, Sims J, Snodin DJ. Sucralose metabolism and pharmacokinetics in man. Food Chem Toxicol 2000;38(Supplement 2):31-41.
22. Magnuson BA, Carakostas MC, Moore NH, Poulos SP, Renwick AG. Biological fate of low-calorie sweeteners. Nutr Rev 2016;74(11):670-89.
23. Jang H-J, Kokrashvili Z, Theodorakis MJ, Carlson OD, Kim BJ, Zhou J, Kim HH, Xu X, Chan SL, Juhaszova M, et al. Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1. Proc Natl Acad Sci U S A 2007;104(38):15069-74.
24. Nakagawa Y, Nagasawa M, Yamada S, Hara A, Mogami H, Nikolaev VO, Lohse MJ, Shigemura N, Ninomiya Y, Kojima I. Sweet taste receptor expressed in pancreatic β-cells activates the calcium and cyclic AMP signaling systems and stimulates insulin secretion. PLoS One 2009;4(4):e5106.
25. +-channel activity. Metabolism 2000;49(2): 208-14.
26. Fujita Y, Wideman RD, Speck M, Asadi A, King DS, Webber TD, Haneda M, Kieffer TJ. Incretin release from gut is acutely enhanced by sugar but not by sweeteners in vivo. Am J Physiol Endocrinol Metab 2009;296(3):E473.
27. Ludwig DS, Majzoub JA, Al-Zahrani A, Dallal GE, Blanco I, Roberts SB. High glycemic index foods, overeating, and obesity. Pediatrics 1999;103(3):e26.
28. Tellez LA, Han W, Zhang X, Ferreira TL, Perez IO, Shammah-Lagnado SJ, van den Pol AN, de Araujo IE. Separate circuitries encode the hedonic and nutritional values of sugar. Nat Neurosci 2016;19(3):465-70.
29. Smeets PA, Weijzen P, de Graaf C, Viergever MA. Consumption of caloric and non-caloric versions of a soft drink differentially affects brain activation during tasting. Neuroimage 2011;54(2):1367-74.
30. Murray S, Tulloch A, Criscitelli K, Avena NM. Recent studies of the effects of sugars on brain systems involved in energy balance and reward: relevance to low calorie sweeteners. Physiol Behav 2016;164:504-8.
31. Griffioen-Roose S, Smeets PAM, Weijzen PLG, van Rijn I, van den Bosch I, de Graaf C. Effect of replacing sugar with non-caloric sweeteners in beverages on the reward value after repeated exposure. PLoS One 2013;8(11):e81924.
32. Kant AK, Graubard BI, Atchison EA. Intakes of plain water, moisture in foods and beverages, and total water in the adult US population-nutritional, meal pattern, and body weight correlates: National Health and Nutrition Examination Surveys 1999-2006. Am J Clin Nutr 2009;90(3):655-63.
33. Han E, Powell LM. Consumption patterns of sugar-sweetened beverages in the United States. J Acad Nutr Diet 2013;113(1):43-53.
34. FDA. Additional information about high-intensity sweeteners permitted for use in food in the United States [Internet]. 2018. Available from: https://www.fda.gov/Food/IngredientsPackagingLabeling/FoodAdditivesIngredients/ucm397725.htm.
35. Dalla Man C, Campioni M, Polonsky KS, Basu R, Rizza RA, Toffolo G, Cobelli C. Two-hour seven-sample oral glucose tolerance test and meal protocol: minimal model assessment of β-cell responsivity and insulin sensitivity in nondiabetic individuals. Diabetes 2005;54(11):3265-73.
36. Black AE. Critical evaluation of energy intake using the Goldberg cut-off for energy intake:basal metabolic rate. A practical guide to its calculation, use and limitations. Int J Obes 2000;24(9):1119.
37. McArdle WD. Exercise physiology: energy, nutrition, and human performance. 6th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2007.
38. Baecke JA, Burema J, Frijters JE. A short questionnaire for the measurement of habitual physical activity in epidemiological studies. Am J Clin Nutr 1982;36(5):936-42.
39. Flint A, Raben A, Blundell JE, Astrup A. Reproducibility, power and validity of visual analogue scales in assessment of appetite sensations in single test meal studies. Int J Obes Relat Metab Disord 2000;24(1):38-48.
40. Logue C, Dowey LRC, Strain JJ, Verhagen H, McClean S, Gallagher AM. Application of liquid chromatography-tandem mass spectrometry to determine urinary concentrations of five commonly used low-calorie sweeteners: a novel biomarker approach for assessing recent intakes? J Agric Food Chem 2017;65(22):4516-25.
41. Sharma RS, Joy RC, Boushey CJ, Ferruzzi MG, Leonov AP, McCrory MA. Effects of para-aminobenzoic acid (PABA) form and administration mode on PABA recovery in 24-hour urine collections. J Acad Nutr Diet 2014;114(3):457-63.
42. Hedrick VE, Savla J, Comber DL, Flack KD, Estabrooks PA, Nsiah-Kumi PA, Ortmeier S, Davy BM. Development of a brief questionnaire to assess habitual beverage intake (BEVQ-15): sugar-sweetened beverages and total beverage energy intake. J Acad Nutr Diet 2012;112(6):840-9.
43. Raben A, Vasilaras TH, Møller AC, Astrup A. 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 2002;76(4):721-9.
44. Colditz GA, Willett WC, Stampfer MJ, London SJ, Segal MR, Speizer FE. Patterns of weight change and their relation to diet in a cohort of healthy women. Am J Clin Nutr 1990;51(6):1100-5.
45. Parker DR, Gonzalez S, Derby CA, Gans KM, Lasater TM, Carleton RA. Dietary factors in relation to weight change among men and women from two southeastern New England communities. Int J Obes Relat Metab Disord 1997;21(2):103-9.
46. Malhotra R, Ostbye T, Riley CM, Finkelstein EA. Young adult weight trajectories through midlife by body mass category. Obesity (Silver Spring) 2013;21(9):1923-34.
47. Fedewa MV, Das BM, Evans EM, Dishman RK. Change in weight and adiposity in college students: a systematic review and meta-analysis. Am J Prev Med 2014;47(5):641-52.
48. BCC Research. The market for high-intensity sweeteners is expected to reach nearly $1.9 billion in 2017 [Internet]. 2013. Available from: https://www.bccresearch.com/pressroom/fod/market-high-intensitysweeteners-expected-reach-nearly-$1.9-billion-2017.
49. Baird IM, Shephard NW, Merritt RJ, Hildick-Smith G. Repeated dose study of sucralose tolerance in human subjects. Food Chem Toxicol 2000;38(Supplement 2):123-9.
50. Blackburn GL, Kanders BS, Lavin PT, Keller SD, Whatley J. The effect of aspartame as part of a multidisciplinary weight-control program on short- and long-term control of body weight. Am J Clin Nutr 1997;65(2):409-18.
51. Maersk M, Belza A, Stodkilde-Jorgensen H, Ringgaard S, Chabanova E, Thomsen H, Pedersen SB, Astrup A, Richelsen B. Sucrose-sweetened beverages increase fat storage in the liver, muscle, and visceral fat depot: a 6-mo randomized intervention study. Am J Clin Nutr 2012;95(2):283-9.
52. 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(4):650-7.
53. Maki KC, Curry LL, Carakostas MC, Tarka SM, Reeves MS, Farmer MV, McKenney JM, Toth PD, Schwartz SL, Lubin BC, et al. The hemodynamic effects of rebaudioside A in healthy adults with normal and low-normal blood pressure. Food Chem Toxicol 2008;46(7, Supplement):S40-S6.
54. Hsieh MH, Chan P, Sue YM, Liu JC, Liang TH, Huang TY, Tomlinson B, Chow MS, Kao PF, Chen YJ. Efficacy and tolerability of oral stevioside in patients with mild essential hypertension: a two-year, randomized, placebo-controlled study. Clin Ther 2003;25(11):2797-808.
55. 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 2013;346:e7492.
56. Hall KD, Sacks G, Chandramohan D, Chow CC, Wang YC, Gortmaker SL, Swinburn BA. Quantification of the effect of energy imbalance on bodyweight. Lancet 2011;378(9793):826-37.
57. Reid M, Hammersley R, Hill AJ, Skidmore P. Long-term dietary compensation for added sugar: effects of supplementary sucrose drinks over a 4-week period. Br J Nutr 2007;97(1):193-203.
58. Gadah NS, Brunstrom JM, Rogers PJ. Cross-over studies underestimate energy compensation: the example of sucrose-versus sucralose-containing drinks. Appetite 2016;107:398-405.
59. Almiron-Roig E, Palla L, Guest K, Ricchiuti C, Vint N, Jebb SA, Drewnowski A. Factors that determine energy compensation: a systematic review of preload studies. Nutr Rev 2013;71(7):458-73.
60. DiMeglio DP, Mattes RD. Liquid versus solid carbohydrate: effects on food intake and body weight. Int J Obes Relat Metab Disord 2000;24(6):794-800.
61. Mattes RD, Shikany JM, Kaiser KA, Allison DB. Nutritively sweetened beverage consumption and body weight: a systematic review and meta-analysis of randomized experiments. Obes Rev 2011;12(5):346.
62. McGregor IS, Lee AM. Metabolic changes associated with ingestion of different macronutrients and different meal sizes in rats. Physiol Behav 1995;57(2):277-86.
63. Tucker RM, Tan, S-Y. Do non-nutritive sweeteners influence acute glucose homeostasis in humans? A systematic review. Physiol Behav 2017;182:17-26.
64. Sylvetsky AC, Brown RJ, Blau JE, Walter M, Rother KI. Hormonal responses to non-nutritive sweeteners in water and diet soda. Nutr Metab 2016;13(1):71.
65. Wu T, Bound MJ, Standfield SD, Bellon M, Young RL, Jones KL, Horowitz M, Rayner CK. Artificial sweeteners have no effect on gastric emptying, glucagon-like peptide-1, or glycemia after oral glucose in healthy humans. Diabetes Care 2013;36(12):e202.
66. Mars M, Stafleu A, de Graaf C. Use of satiety peptides in assessing the satiating capacity of foods. Physiol Behav 2012;105(2):483-8.
67. Malik VS, Popkin BM, Bray GA, Després J-P, Willett WC, Hu FB. Sugar-sweetened beverages and risk of metabolic syndrome and type 2 diabetes: a meta-analysis. Diabetes Care 2010;33(11): 2477-83.
68. Suez J, Korem T, Zilberman-Schapira G, Segal E, Elinav E. Non-caloric artificial sweeteners and the microbiome: findings and challenges. Gut Microbes 2015;6(2):149-55.
69. Suez J, Korem T, Zeevi D, Zilberman-Schapira G, Thaiss CA, Maza O, Israeli D, Zmora N, Gilad S, Weinberger A. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature 2014;514:181-6.
70. Uebanso T, Ohnishi A, Kitayama R, Yoshimoto A, Nakahashi M, Shimohata T, Mawatari K, Takahashi A. Effects of low-dose noncaloric sweetener consumption on gut microbiota in mice. Nutrients 2017;9(6):560.
71. Abou-Donia MB, El-Masry EM, Abdel-Rahman AA, McLendon RE, Schiffman SS. Splenda alters gut microflora and increases intestinal p-glycoprotein and cytochrome p-450 in male rats. J Toxicol Environ Health A 2008;71(21):1415-29.
72. Palmnas MS, Cowan TE, Bomhof MR, Su J, Reimer RA, Vogel HJ, Hittel DS, Shearer J. Low-dose aspartame consumption differentially affects gut microbiota-host metabolic interactions in the diet-induced obese rat. PLoS One 2014;9(10):e109841.
73. Wooley OW, Wooley SC, Dunham RB. Calories and sweet taste: effects on sucrose preference in the obese and nonobese. Physiol Behav 1972;9(5):765-8.
74. Shide DJ, Rolls BJ. Information about the fat content of preloads influences energy intake in healthy women. J Am Diet Assoc 1995;95(9):993-8.
75. Hill RJ, Davies PSW. The validity of self-reported energy intake as determined using the doubly labelled water technique. Br J Nutr 2001;85(4):415-30.
76. Renwick AG. The use of a sweetener substitution method to predict dietary exposures for the intense sweetener rebaudioside A. Food Chem Toxicol 2008;46(7, Supplement):S61-S9.
77. Fernstrom JD. Non-nutritive sweeteners and obesity. Annu Rev Food Sci Technol 2015;6:119-36.
78. Kuhn C, Bufe B, Winnig M, Hofmann T, Frank O, Behrens M, Lewtschenko T, Slack JP, Ward CD, Meyerhof W. Bitter taste receptors for saccharin and acesulfame K. J Neurosci 2004;24(45):10260-5.