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The effects of low-calorie sweeteners on energy intake and body weight: a systematic review and meta-analyses of sustained intervention studies


Previous meta-analyses of intervention studies have come to different conclusions about effects of consumption of low-calorie sweeteners (LCS) on body weight. The present review included 60 articles reporting 88 parallel-groups and cross-over studies ≥1 week in duration that reported either body weight (BW), BMI and/or energy intake (EI) outcomes. Studies were analysed according to whether they compared (1) LCS with sugar, (2) LCS with water or nothing, or (3) LCS capsules with placebo capsules. Results showed an effect in favour of LCS vs sugar for BW (29 parallel-groups studies, 2267 participants: BW change, −1.06 kg, 95% CI −1.50 to −0.62, I2 = 51%), BMI and EI. Effect on BW change increased with ‘dose’ of sugar replaced by LCS, whereas there were no differences in study outcome as a function of duration of the intervention or participant blinding. Overall, results showed no difference in effects of LCS vs water/nothing for BW (11 parallel-groups studies, 1068 participants: BW change, 0.10 kg, 95% CI −0.87 to 1.07, I2 = 82%), BMI and EI; and inconsistent effects for LCS consumed in capsules (BW change: −0.28 kg, 95% CI −0.80 to 0.25, I2 = 0%; BMI change: 0.20 kg/m2, 95% CI 0.04 to 0.36, I2 = 0%). Occurrence of adverse events was not affected by the consumption of LCS. The studies available did not permit robust analysis of effects by LCS type. In summary, outcomes were not clearly affected when the treatments differed in sweetness, nor when LCS were consumed in capsules without tasting; however, when treatments differed in energy value (LCS vs sugar), there were consistent effects in favour of LCS. The evidence from human intervention studies supports the use of LCS in weight management, constrained primarily by the amount of added sugar that LCS can displace in the diet.

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Fig. 1
Fig. 2: Forest plots showing individual and overall standardised mean differences (SMD) for the effects of LCS vs sugar for ΔBW and EI measured in parallel-groups studies (random effects models).
Fig. 3: Forest plots showing individual and overall standardised mean differences (SMD) for the effects of LCS vs water/nothing for ΔBW and EI measured in parallel-groups studies (random effects models).
Fig. 4: Forest plots showing individual and overall standardised mean differences (SMD) for the effects of LCS capsules vs placebo capsules for ΔBW and ΔBMI measured in parallel-groups studies (random effects models).


  1. 1.

    Buyken A, Mela D, Dussort P, Johnson I, Macdonald I, Stowell J, et al. Dietary carbohydrates: a review of international recommendations and the methods used to derive them. Eur J Clin Nutr. 2018;72:1625–43.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. 2.

    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. 2008;16:1894–900.

    PubMed  Google Scholar 

  3. 3.

    Swithers SE. Not-so-healthy sugar substitutes? Curr Opin. Behav Sci. 2016;9:106–10.

    Google Scholar 

  4. 4.

    Blundell JE, Hill AJ. Intense sweeteners (aspartame) on appetite. Lancet. 1986;8489:1092–3.

    Google Scholar 

  5. 5.

    Swithers SE, Martin AA, Davidson TL. High-intensity sweeteners and energy balance. Physiol Behav. 2010;100:5562.

    Google Scholar 

  6. 6.

    Ludwig DS. Artificially sweetened beverages: cause for concern. JAMA. 2009;302:2477–8.

    PubMed  Google Scholar 

  7. 7.

    Yang Q. Gain weight by ‘going diet’? Artificial sweeteners and the neurobiology of sugar cravings: neuroscience 2010. Yale. J Med Biol. 2010;83:101–8.

    Google Scholar 

  8. 8.

    Rogers PJ. The role of low-calorie sweeteners in the prevention and management of overweight and obesity: evidence v. conjecture. Proc Nutr Soc. 2018;77:230–8.

    PubMed  Google Scholar 

  9. 9.

    Appleton KM, Tuorila H, Bertenshaw EJ, de Graaf C, Mela DJ. Sweet taste exposure and the subsequent acceptance and preference for sweet taste in the diet: systematic review of the published literature. Am J Clin Nutr. 2018;107:405419.

    Google Scholar 

  10. 10.

    Rogers PJ, Hogenkamp PS, de Graaf C, Higgs S, Lluch A, Ness AR, 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. 2016;40:381–94.

    CAS  Google Scholar 

  11. 11.

    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;100:765–77.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Azad MB, Abou-Setta AM, Chauhan BF, Rabbani R, Lys J, Copstein L, et al. Nonnutritive sweeteners and cardiometabolic health: a systematic review and meta-analysis of randomized controlled trials and prospective cohort studies. CMAJ. 2017;189:E929–39.

    PubMed  PubMed Central  Google Scholar 

  13. 13.

    Toews I, Lohner S, Küllenberg de Gaudry D, Sommer H, Meerpohl JJ. Association between intake of non-sugar sweeteners and health outcomes: systematic review and meta-analyses of randomised and non-randomised controlled trials and observational studies. BMJ. 2019;364:k4718.

  14. 14.

    Mela DJ, McLaughlin J, Rogers PJ. Perspective: standards for research and reporting on low-energy (“artificial”) sweeteners. Adv Nutr. 2020;11:484–91.

    PubMed  Google Scholar 

  15. 15.

    Rogers PJ, Ferriday D, Irani B, Hoi JKH, England CY, Bajwa KK, et al. Sweet satiation: acute effects of consumption of sweet drinks on appetite for and intake of sweet and non-sweet foods. Appetite. 2020;149:104631.

    PubMed  Google Scholar 

  16. 16.

    Hunter SR, Reister EJ, Cheon E, Mattes RD. Low calorie sweeteners differ in their physiological effects in humans. Nutrients. 2019;11:2717.

    CAS  PubMed Central  Google Scholar 

  17. 17.

    Rogers PJ. Combating excessive eating: a role for four evidenced-based remedies. Obesity. 2018;26:S18–S24.

    PubMed  Google Scholar 

  18. 18.

    Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JPA, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009;339:b2700.

    PubMed  PubMed Central  Google Scholar 

  19. 19.

    Mattes RD. Low calorie sweeteners: science and controversy: conference proceedings. Phyiol Behav. 2016;164:429–31.

    CAS  Google Scholar 

  20. 20.

    European Food Safety Authority. Scientific opinion on dietary reference values for carbohydrates and dietary fibre. EFSA J. 2010;8:1462.

  21. 21.

    Engel S, Tholstrup T, Bruun JM, Astrup A, Richelsen B, Raben A. Effect of high milk and sugar-sweetened and non-caloric soft drink intake on insulin sensitivity after 6 months in overweight and obese adults: a randomized controlled trial. Eur J Clin Nutr. 2018;72:358–66.

    CAS  PubMed  Google Scholar 

  22. 22.

    Engel S, Tholstrup T, Bruun JM, Astrup A, Richelsen B, Raben A. Correction: Effect of high milk and sugar-sweetened and noncaloric soft drink intake on insulin sensitivity after 6 months in overweight and obese adults: a randomized controlled trial. Eur J Clin Nutr. 2020;74:210–13.

    PubMed  Google Scholar 

  23. 23.

    Higgins KA, Mattes RD. A randomized controlled trial contrasting the effects of 4 low-calorie sweeteners and sucrose on body weight in adults with overweight or obesity. Am J Clin Nutr. 2019;109:1288–301.

    PubMed  Google Scholar 

  24. 24.

    Tate DF, Turner-McGrievy G, Lyons E, Stevens J, Erickson K, Polzien K, et al. Replacing caloric beverages with water or diet beverages for weight loss in adults: main results of the Choose Healthy Options Consciously Everyday (CHOICE) randomized clinical trial. Am J Clin Nutr. 2012;95:555–63.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. 25.

    Piernas C, Tate DF, Wang X, Popkin BM. Does diet-beverage intake affect dietary composition patterns? Results from the Choose Healthy Options Consciously Everyday (CHOICE) randomized trial. Am J Clin Nutr. 2013;97:604–11.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. 26.

    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;65:409–18.

    CAS  PubMed  Google Scholar 

  27. 27.

    Madjd A, Taylor MA, Delavari A, Malekzadeh R, Macdonald IA, Farshchi HR. Effects of replacing diet beverages with water on weight loss and weight maintenance: 18-month follow-up, randomized clinical trial. Int J Obes. 2018;42:835–40.

    CAS  Google Scholar 

  28. 28.

    Reid M, Hammersley R, Duffy M, Ballantyne C. Effects on obese women of the sugar sucrose added to the diet over 28 d: a quasi-randomised, single-blind, controlled trial. Br J Nutr. 2014;111:563–70.

    CAS  PubMed  Google Scholar 

  29. 29.

    Reid M, Hammersley R, Duffy M. Effects of sucrose drinks on macronutrient intake, body weight, and mood state in overweight women over 4 weeks. Appetite. 2010;55:130–6.

    CAS  PubMed  Google Scholar 

  30. 30.

    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;97:193–203.

    CAS  PubMed  Google Scholar 

  31. 31.

    Ebbeling CB, Feldman HA, Chomitz VR, Antonelli TA, Osganian SK, Ludwig DS. A randomized trial of sugar-sweetened beverages and adolescent body weight. N Engl J Med. 2012;367:1407–16.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. 32.

    Ebbeling CB, Feldman HA, Osganian SK, Chomitz VR, Ellenbogen SJ, Ludwig DS. Effects of decreasing sugar-sweetened beverage consumption on body weight in adolescents: a randomized, controlled pilot study. Pediatrics. 2006;117:673–80.

    PubMed  Google Scholar 

  33. 33.

    Kochhar A, Dhindsa S, Sachdeva R. Effect of stevia leaf (Stevia rebaudiana) powder supplementation and nutrition counselling on anthropometric parameters and gain in knowledge of the subjects. Studies on Ethno-Medicine. 2008;2:107–13.

    Google Scholar 

  34. 34.

    Higgins JPT, Green S. Cochrane handbook for systematic reviews of interventions. 5.1 edn. Chichester, UK: The Cochrane Collaboration & John Wiley & Sons, Ltd; 2011.

  35. 35.

    Deeks JJ, Altman DG, Bradburn MJ. Statistical methods for examining heterogeneity and combining results from several studies in meta-analysis. In: Egger M, Davey Smith G, Altman DG, editors. Systematic reviews in health care: meta-analysis in context. London: BMJ Publishing Group; 2001. pp. 285–312.

  36. 36.

    Egger M, Davey Smith G. Principles of and procedures for systematic reviews. In: Egger M, Davey Smith G, Altman DG, editors Systematic reviews in health care: meta-analysis in context. London: BMJ Publishing Group; 2001. pp. 23-42.

  37. 37.

    Furukawa TA, Barbui C, Cipriani A, Brambilla P, Watanabe N. Imputing missing standard deviations in meta-analyses can provide accurate results. J Clin Epidemiol. 2006;59:7–10.

    PubMed  Google Scholar 

  38. 38.

    Higgins JPT, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–58.

    PubMed  Google Scholar 

  39. 39.

    Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2004;327:557–60.

    Google Scholar 

  40. 40.

    Sterne JAC, Egger M, Davey Smith G. Investigating and dealing with publication and other biases. In: Egger M, Davey Smith G, Altman DG, editors. Systematic reviews in health care: meta-analysis in context. London: BMJ Publishing Group; 2001. pp. 189–208.

  41. 41.

    de Ruyter JC, Olthof MR, Seidell JC, Katan MB. A trial of sugar-free or sugar-sweetened beverages and body weight in children. N Engl J Med. 2012;367:1397–406.

    PubMed  Google Scholar 

  42. 42.

    Ebbeling CB, Feldman HA, Steltz SK, Quinn NL, Robinson LM, Ludwig DS. Effects of sugar-sweetened, artificially sweetened, and unsweetened beverages on cardiometabolic risk factors, body composition, and sweet taste preference: a randomised controlled trial. J Am Heart Assoc. 2020;9:e015668.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. 43.

    Ludwig DS. Beverages and societal health (BASH III). Identifier: NCT01295671. 2019.

  44. 44.

    Ensor M, Banfield AB, Smith RR, Williams J, Lodder RA. Safety and efficacy of D-tagatose in glycemic control in subjects with type 2 diabetes. J Endocrinol Diabetes Obes. 2015;3:1065.

    PubMed  Google Scholar 

  45. 45.

    Taljaard C, Covic NM, van Graan AE, Kruger HS, Smuts CM, Baumgartner J, et al. Effects of a multi-micronutrient-fortified beverage, with and without sugar, on growth and cognition in South African schoolchildren: a randomised, double-blind, controlled intervention. Br J Nutr. 2013;110:2271–84.

    CAS  PubMed  Google Scholar 

  46. 46.

    Angelopoulos TJ, Lowndes J, Rippe JM. No change in muscle or liver content in adults after 6 months of daily consumption of sugar sweetened or diet beverages. Obes Rev. 2016;17:47. (abstract T3:S17.45)

    Google Scholar 

  47. 47.

    Angelopoulos TJ, Lowndes J, Sinnett SS, Rippe JM. Six months of daily consumption of sugar sweetened beverages or diet beverages does not increase cardiovascular disease risk factors. Obes Rev. 2016;17:48. (abstract T3:S17.46)

    Google Scholar 

  48. 48.

    Vázquez-Duran M, Orea-Tejeda A, Castillo-Martínez L, Cano-García A, Téllez-Olvera L, Keirns-Davis C. A randomized control trial for reduction of caloric and non-caloric sweetened beverages in young adults: effects in weight, body composition and blood pressure. Nutrición Hospitalaria. 2016;2016:1372–8.

    Google Scholar 

  49. 49.

    Frey GH. Use of aspartame by apparently healthy children and adolescents. J Toxicol Environ Health. 1976;2:401–15.

    CAS  PubMed  Google Scholar 

  50. 50.

    McLean Baird I, Shephard NW, Merritt RJ, Hildick-Smith G. Repeated dose study of sucralose tolerance in human subjects. Food Chem Toxicol. 2000;38:S123–9.

    Google Scholar 

  51. 51.

    Sánchez-Delgado M, Antonio Estrada JA, Paredes-Cervantes V, Kaufer-Horwitz M, Contreras I. Changes in nutrient and calorie intake, adipose mass, triglycerides and TNF-α concentrations after non-caloric sweetener intake: pilot study. Int J Vitam Nutr Res. 2019;28: 1-12.

  52. 52.

    Campos V, Despland C, Brandejsky V, Kreis R, Schneiter P, Chiolero A, et al. Sugar- and artificially sweetened beverages and intrahepatic fat: a randomized controlled trial. Obesity. 2015;23:2335–9.

    CAS  PubMed  Google Scholar 

  53. 53.

    Raben A, Vasilaras TH, Møller AC, Astrup A. Sucrose compared with artificial sweeteners: different effects on ad libitum food intake and body weight after 10wk of supplementation in overweight subjects. Am J Clin Nutr. 2002;76:721–9.

    CAS  PubMed  Google Scholar 

  54. 54.

    Berryman GH, Hazel GR, Taylor JD, Sanders PG, Weinberg MS. A case for safety of cyclamate and cyclamate-saccharin combinations. Am J Clin Nutr. 1968;21:673–87.

    Google Scholar 

  55. 55.

    Addington EE, Grunewald KK. Aspartame- or sugar-sweetened beverages: effects on weight gain, appetite, and food intake in young women. FASEB J. 1988;2:A1197. (abstract 5239)

    Google Scholar 

  56. 56.

    Kim EJ, Kim MY, Kim J-S, Cho K-D, Han C-K, Lee B-H. Effects of fructooligosaccharides intake on body weight, lipid profiles, and calcium status among Korean college students. FASEB J. 2011;25.

  57. 57.

    Stanhope KL, Medici V, Bremer AA, Lee V, Lam HD, Nunez MV, et al. A dose-response study of consuming high-fructose corn syrup-sweetened beverages on lipid/lipoprotein risk factors for cardiovascular disease in young adults. Am J Clin Nutr. 2015;101:1144–54.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. 58.

    Reid M, Hammersley R. The effects of blind substitution of aspartame-sweetened for sugar-sweetened soft drinks on appetite and mood. Br Food J. 1998;100:254–9.

    Google Scholar 

  59. 59.

    Maersk M, Belza A, Stødkilde-Jørgensen H, Ringgaard S, Chabanova E, Thomsen H, et al. 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;95:283–9.

    CAS  PubMed  Google Scholar 

  60. 60.

    Njike VY, Faridi Z, Shuval K, Dutta S, Kay CD, West SG, et al. Effects of sugar-sweetened and sugar-free cocoa on endothelial function in overweight adults. Int J Cardiol. 2011;149:83–8.

    PubMed  Google Scholar 

  61. 61.

    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;50:474–8.

    CAS  PubMed  Google Scholar 

  62. 62.

    Werner D, Emmett PM, Heaton KW. Effects of dietary sucrose on factors influencing cholesterol gall stone formation. Gut. 1984;25:269–74.

    CAS  PubMed  PubMed Central  Google Scholar 

  63. 63.

    Chantelau EA, Gösseringer G, Sonnenberg GE, Berger M. Moderate intake of sucrose does not impair metabolic control in pump-treated diabetic out-patients. Diabetologia. 1985;28:204–7.

    CAS  PubMed  Google Scholar 

  64. 64.

    Wolraich ML, Lindgren SD, Stumbo PJ, Stegink LD, Appelbaum MI, Kiritsy MC. Effects of diets high in sucrose or aspartame on the behavior and cognitive performance of children. N Engl J Med. 1994;330:301–7.

    CAS  PubMed  Google Scholar 

  65. 65.

    Tordoff MG, Alleva AM. Effect of drinking soda sweetened with aspartame or high-fructose corn syrup on food intake and body weight. Am J Clin Nutr. 1990;51:963–9.

    CAS  PubMed  Google Scholar 

  66. 66.

    Naismith DJ, Rhodes C. Adjustment in energy intake following the covert removal of sugar from the diet. J Hum Nutr Diet. 1995;8:167–75.

    Google Scholar 

  67. 67.

    Kuzma JN, Cromer G, Hagman DK, Breymeyer KL, Roth CL, Foster-Schubert KE, et al. No difference in ad libitum energy intake in healthy men and women consuming beverages sweetened with fructose, glucose, or high-fructose corn syrup: a randomized trial. Am J Clin Nutr. 2015;102:1373–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  68. 68.

    Al-Dujaili EAS, Twaij H, Bataineh YA, Arshad U, Amjid F. Effect of stevia consumption on blood pressure, stress hormone levels and anthropometrical parameters in healthy persons. Am J Pharmacol Toxicol. 2017;12:7–17.

    CAS  Google Scholar 

  69. 69.

    Peters JC, Beck J, Cardel M, Wyatt HR, Foster GD, Pan Z, et al. The effects of water and non-nutritive sweetened beverages on weight loss and weight maintenance: a randomized clinical trial. Obesity. 2016;24:297–304.

    PubMed  Google Scholar 

  70. 70.

    Madjd A, Taylor MA, Delavari A, Malekzadeh R, Macdonald IA, Farshchi HR. Beneficial effects of replacing diet beverages with water on type 2 diabetic obese women following a hypo-energetic diet: a randomized, 24-week clinical trial. Diabetes Obes Metab. 2016;19:125–32.

    PubMed  Google Scholar 

  71. 71.

    Stamataki N, Crooks B, McLaughlin J. Daily consumption of stevia drop effects on glycemia, body weight and energy intake: Results from a 12-week, open-label, randomized controlled trial in healthy adults. Curr Dev Nutr. 2020;4:663.

    PubMed Central  Google Scholar 

  72. 72.

    Higgins KA, Conisidine 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;148:650–7.

    PubMed  Google Scholar 

  73. 73.

    Kanders BS, Lavin PT, Kowalchuk MB, Greenberg I, Blackburn GL. An evaluation of the effect of aspartame on weight loss. Appetite. 1988;11:73–84.

    PubMed  Google Scholar 

  74. 74.

    Bueno-Hernández N, Esquivel-Velázquez M, Alcántara-Suárez R, Gómez-Arauz AY, Espinosa-Flores AJ, de León-Barrera KL, et al. Chronic sucralose consumption induces elevation of serum insulin in young healthy adults: a randomized, double blind, controlled trial. Nutr J. 2020;19:32.

    PubMed  PubMed Central  Google Scholar 

  75. 75.

    Fantino M, Fantino A, Matray M, Mistretta F. Beverages containing low energy sweeteners do not differ from water in their effects on appetite, energy intake and food choices in healthy, non-obese French adults. Appetite. 2018;125:557–65.

    PubMed  Google Scholar 

  76. 76.

    Koyuncu BU, Balci MK. Metabolic effects of dissolved aspartame in the mouth before meals in prediabetic patients; a randomized controlled cross-over study. J Endocrinol Diabetes Obes. 2014;2:1032.

    Google Scholar 

  77. 77.

    Bonnet F, Tavenard A, Esvan M, Laviolle B, Viltard M, Lepicard EM, 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;148:1293–9.

    PubMed  Google Scholar 

  78. 78.

    Hsieh M-H, Chan P, Sue Y-M, Liu J-C, Liang TH, Huang T-Y, et al. Efficacy and tolerability of oral stevioside in patients with mild essential hypertension: a two-year, randomized, placebo-controlled study. Clin Ther. 2003;25:2797–808.

    CAS  PubMed  Google Scholar 

  79. 79.

    Chan P, Tomlinson B, Chen Y-J, Liu J-C, Hsieh M-H, Cheng J-T. A double-blind placebo-controlled study of the effectiveness and tolerability of oral stevioside in human hypertension. Br J Clin Pharmacol. 2000;50:215–20.

    CAS  PubMed  PubMed Central  Google Scholar 

  80. 80.

    Ferri LAF, Alves-Do-Prado W, Yamada SS, Gazola S, Batista MR, Bazotte RB. Investigation of the antihypertensive effect of oral crude stevioside in patients with mild essential hypertension. Phytother Res. 2006;20:732–6.

    CAS  PubMed  Google Scholar 

  81. 81.

    Leon AS, Hunninghake DB, Bell C, Rassin DK, Tephly TE. Safety of long-term large doses of aspartame. Arch Int Med. 1989;149:2318–24.

    CAS  Google Scholar 

  82. 82.

    Maki KC, Curry LL, Reeves MS, Toth PD, McKenney JM, Farmer MV, et al. Chronic consumption of rebaudioside A, a steviol glycoside, in men and women with type 2 diabetes mellitus. Food Chem Toxicol. 2008;46:S47–53.

    CAS  PubMed  Google Scholar 

  83. 83.

    Rizwan F, Rashid HU, Yesmine S, Monjur F, Chatterjee TK. Preliminary analysis of the effect of Stevia (Stevia rebaudiana) in patients with chronic kidney disease (stage I to stage III). Contemp Clin Trials Commun. 2018;12:17–25.

    PubMed  PubMed Central  Google Scholar 

  84. 84.

    Barriocanal LA, Palacios M, Benitez G, Benitez S, Jimenez JT, Jimenez N, et al. Apparent lack of pharmacological effect of steviol glycosides used as sweeteners in humans. A pilot study of repeated exposures in some normotensive and hypotensive individuals and in Type 1 and Type 2 diabetics. Re Toxicol Pharmacol. 2008;51:37–41.

    CAS  Google Scholar 

  85. 85.

    Knopp RH, Brandt K, Arky RA. Effects of aspartame in young persons during weight reduction. J Toxicol Environ Health. 1976;2:417–28.

    CAS  PubMed  Google Scholar 

  86. 86.

    Stern SB, Bleicher SJ, Flores A, Gombos G, Recitas D, Shu J. Administration of aspartame in non-insulin-dependent diabetics. J Toxicol Environ Health. 1976;2:429–39.

    CAS  PubMed  Google Scholar 

  87. 87.

    da Silva GEC, Assef AH, Albino CC, Ferri LAF, Tasin G, Takahashi MH, et al. Investigation of the tolerability of oral stevioside in Brazilian hyperlipidemic patients. Braz Arch Biol Technol. 2006;49:583–7.

    Google Scholar 

  88. 88.

    Maki KC, Curry LL, Carakostas MC, Tarka SM, Reeves MS, Farmer MV, et al. (2008). The hemodynamic effects of rebaudioside A in healthy adults with normal and low-normal blood pressure. Food Chem Toxicol. 2008;46:S40–6.

    CAS  PubMed  Google Scholar 

  89. 89.

    Thomson P, Santibañez R, Aguirre C, Galgani JE. Short-term impact of sucralose consumption on the metabolic response and gut microbiome of healthy adults. Br J Nutr. 2019;122:856–62.

    CAS  PubMed  Google Scholar 

  90. 90.

    Lertrit A, Srimachai S, Saetung S, Chanprasertyothin S, Chailurkit L-O, Areevut C, et al. Effects of sucralose on insulin and glucagon-like peptide-1 secretion in healthy subjects: a randomized, double-blind, placebo-controlled trial. Nutr. 2018. 2018;55-56:125–30.

    CAS  Google Scholar 

  91. 91.

    Almiron-Roig E, Palla L, Guest K, Ricchiuti C, Vint N, Jebb SA, et al. Factors that determine energy compensation: a systematic review of preload studies. Nutr Rev. 2013;71:458–73.

    PubMed  PubMed Central  Google Scholar 

  92. 92.

    Hall KD, Guo J. Obesity energetics: body weight regulation and the effects of diet composition. Gastroenterology. 2017;152:1718–27.

    PubMed  PubMed Central  Google Scholar 

  93. 93.

    Polidori D, Sanghvi A, Seeley RJ, Hall KD. How strongly does appetite counter weight loss? Quantification of feedback control of human energy intake. Obesity. 2016;24:2289–95.

    CAS  PubMed  Google Scholar 

  94. 94.

    Laviada-Molina H, Molina-Segui F, Pérez-Gaxiola G, Cuello-García C, Arjona-Villicaña R, Espinosa-Marrón A, et al. Effects of nonnutritive sweeteners on body weight and BMI in diverse clinical contexts: Systematic review and meta-analysis. Obes Rev. 2020;21:e13020.

    PubMed  Google Scholar 

  95. 95.

    Morenga LT, Mallard S, Mann J. Dietary sugars and body weight: systematic review and meta-analyses of randomised controlled trials and cohort studies. BMJ. 2012;345:e7492.

    Google Scholar 

  96. 96.

    Sievenpiper JL, Khan TA, Ha V, Viguiliouk E, Auyeung R. The importance of study design in the assessment of non-nutritive sweeteners and cardiometabolic health. CMAJ. 2017;189:E1424–5.

    PubMed  PubMed Central  Google Scholar 

  97. 97.

    Masic U, Harrold JA, Christiansen P, Cuthbertson DJ, Hardman CA, Robinson E, et al. EffectS of non-nutritive sWeetened beverages on appetITe during aCtive weigHt loss (SWITCH): Protocol for a randomized, controlled trial assessing the effects of non-nutritive sweetened beverages compared to water during a 12-week weight loss period and a follow up weight maintenance period. Contemp Clin Trials. 2017;53:80–8.

    CAS  PubMed  Google Scholar 

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We are grateful to authors we contacted who supplied us with results and other information about their studies. This research was supported by the School of Psychological Science, University of Bristol, and the Department of Psychology, Faculty of Science and Technology, Bournemouth University. Part of this research was supported by the NIHR (National Institute for Health Research) Biomedical Research Centre at University Hospitals Bristol NHS Foundation Trust and the University of Bristol. These Institutions played no role in the design of the research, the collection and analysis of data or the decision to publish. The views expressed in this publication are those of the authors and not necessarily those of the NHS, NIHR, or the Department of Health and Social Care.

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Correspondence to Peter J. Rogers.

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In connection with research on LCS and sugar, PJR. has received funding for research from Sugar Nutrition UK; provided consultancy services for Coca-Cola Great Britain; received speaker’s fees from the International Sweeteners Association, the Global Stevia Research Institute, ILSI-Brasil, ILSI-Europe and ILSI-India; and received honoraria from ILSI-Europe. KMA has received funding for relevant research from Unilever R&D Vlaardingen, NL; has current funding from TIFN, NL (in collaboration with Arla Foods, DK, American Beverage Association, USA, Cargill, USA, Dutch Knowledge Centre for Sugar, NL, Firmenich, CH, the International Sweeteners Association, BE, SinoSweet, China, Unilever, NL), and from the International Sweeteners Association; and has received speaker’s expenses from the International Sweeteners Association, PepsiCo and ILSI-North America.

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Rogers, P.J., Appleton, K.M. The effects of low-calorie sweeteners on energy intake and body weight: a systematic review and meta-analyses of sustained intervention studies. Int J Obes 45, 464–478 (2021).

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