Low/no calorie sweeteners do not affect glycaemic response

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ISA statement in response to new study by Suez, Elinav et al.

Brussels, 19th August 2022:  Contrary to outcomes of a new study by Suez, Elinav, et al.1 on low/no calorie sweeteners and gut microbiota, the International Sweeteners Association (ISA) would like to point to collective evidence from clinical trials showing that low/no calorie sweeteners do not adversely affect glycaemic control.2,3,4,5,6

The conclusions presented by Suez, Elinav et al in the press release of the new unblinded randomised controlled trial (RCT) that “some [low/no calorie sweeteners] can alter human consumers’ microbiomes in a way that can change their blood sugar levels” is not supported by results of numerous clinical trials and systematic reviews of RCTs,2-6 examining a range of low/no calorie sweeteners’ intakes and study conditions, and showing lack of effect of low/no calorie sweeteners on glycaemia. Differences in blood glucose reported in this study of healthy individuals may reflect inter- and intra-individual differences in glycaemic responses to a home-performed glucose tolerance test. Moreover, the clinical significance or long-term relevance of small, highly personalised, deviations in blood glucose levels of healthy individuals is questionable, especially since long-term gold-standard glucose control marker (HbA1c) and other health markers were not affected by low/no calorie sweeteners in comparison to control groups. No conclusions about the effects of low/no calorie sweeteners on glucose control or overall health can be extrapolated from this study for the general population or for people who typically consume sweeteners, including people living with diabetes.

In contrast to the hypothesis made by the authors that low/no calorie sweeteners can affect human metabolism by alteration of the intestinal microbiome, a recent review of the literature concluded that there is clear evidence that changes in the diet unrelated to low/no calorie sweeteners consumption are likely the major determinants of change in gut microbiota.7 Indeed, participants’ diet, while recorded, was not fully controlled in this study. Therefore, the impact of dietary intake aspects beyond energy and nutrient intakes, such as intake of specific foods, which have been shown to induce changes in the gut microbiota composition8, cannot be ruled out. A lack of effect of different low/no calorie sweeteners on the microbiome is also supported by the results of recent human clinical studies.9,10,11 This is line with scientific opinions of regulatory authorities worldwide which have repeatedly confirmed the safety of all approved low/no calorie sweeteners12,13,14, including no adverse effect of low/no calorie sweeteners on gut microbiota.

At a time when obesity and non-communicable diseases including diabetes and dental diseases remain major global health challenges, and in light of current public health recommendations to reduce overall sugar intake, low/no calorie sweeteners can be helpful in creating healthier food environments. They provide people with a wide choice of sweet-tasting options with low or no calories, and thus can be a useful tool, when used in place of sugar and as part of a balanced diet, in helping reduce overall sugar and calorie intake, as well as in managing blood glucose levels.15 Low/no calorie sweeteners are also not fermentable by oral bacteria, which means that they do not contribute to tooth demineralisation, which is one of the reasons for tooth decay.15

  1. Suez J, Cohen Y, Valdés-Mas R, Mor U, Dori-Bachash M, Federici S, Zmora N, Leshem A, Heinemann M, Linevsky R, Zur M, Brik RBZ, Bukimen A, Eliyahu-Miller S, Metz A, Fischbein R, Shariv O, Malitsky S, Itkin M, Stettner N, Harmelin A, Shapiro H, Stein-Thoeringer CK, Segal E, Elinav. Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance. Cell 2022. https://doi.org/10.1016/j.cell.2022.07.016
  2. Grotz VL, Pi-Sunyer X, Porte D Jr, Roberts A, Richard Trout J. A 12-week randomized clinical trial investigating the potential for sucralose to affect glucose homeostasis. Regul Toxicol Pharmacol. 2017 Aug;88:22-33
  3. Nichol AD, Holle MJ, An R. Glycemic impact of non-nutritive sweeteners: a systematic review and meta-analysis of randomized controlled trials. Eur J Clin Nutr. 2018 Jun;72(6):796-804
  4. Greyling A, Appleton KM, Raben A, Mela DJ. Acute glycemic and insulinemic effects of low-energy sweeteners: a systematic review and meta-analysis of randomized controlled trials. Am J Clin Nutr. 2020 Oct 1;112(4):1002-1014
  5. McGlynn ND, Khan TA, Wang L, Zhang R, Chiavaroli L, Au-Yeung F, Lee JJ, Noronha JC, Comelli EM, Blanco Mejia S, Ahmed A, Malik VS, Hill JO, Leiter LA, Agarwal A, Jeppesen PB, Rahelic D, Kahleová H, Salas-Salvadó J, Kendall CWC, Sievenpiper JL. Association of Low- and No-Calorie Sweetened Beverages as a Replacement for Sugar-Sweetened Beverages With Body Weight and Cardiometabolic Risk: A Systematic Review and Meta-analysis. JAMA Network Open 2022 Mar 1;5(3):e222092
  6. Rios-Leyvraz M, Montez J (World Health Organization)‎. Health effects of the use of non-sugar sweeteners: a systematic review and meta-analysis. World Health Organization (WHO) 2022. https://apps.who.int/iris/handle/10665/353064. License: CC BY-NC-SA 3.0 IGO
  7. Lobach A, Roberts A, Rowland I. Assessing the in vivo data on low/no-calorie sweeteners and the gut microbiota. Food and Chemical Toxicology 2019; 124: 385-399
  8. Hughes RL, Davis CD, Lobach A, Holscher HD. An Overview of Current Knowledge of the Gut Microbiota and Low-Calorie Sweeteners. Nutr Today. 2021 May-Jun;56(3):105-113.
  9. Thomson P, Santibañez R, Aguirre C, Galgani JE, Garrido D. Short-term impact of sucralose consumption on the metabolic response and gut microbiome of healthy adults. Br J Nutr. 2019 Oct 28;122(8):856-862
  10. Ahmad SY, Friel J, Mackay D. The Effects of Non-Nutritive Artificial Sweeteners, Aspartame and Sucralose, on the Gut Microbiome in Healthy Adults: Secondary Outcomes of a Randomized Double-Blinded Crossover Clinical Trial. Nutrients. 2020 Nov 6;12(11):3408
  11. Serrano J, Smith KR, Crouch AL, Sharma V, Yi F, Vargova V, LaMoia TE, Dupont LM, Serna V, Tang F, Gomes-Dias L, Blakeslee JJ, Hatzakis E, Peterson SN, Anderson M, Pratley RE, Kyriazis GA. High-dose saccharin supplementation does not induce gut microbiota changes or glucose intolerance in healthy humans and mice. Microbiome. 2021 Jan 12;9(1):11.
  12. http://www.fao.org/food/food-safety-quality/scientific-advice/jecfa/en/
  13. http://www.efsa.europa.eu/en/topics/topic/sweeteners
  14. High-Intensity Sweeteners | FDA
  15. EFSA Scientific opinion on the substantiation of health claims related to intense sweeteners. EFSA 2011 Journal 9(6): 2229, and 9(4): 2076 and Commission Regulation 432/2012/EU (OJ L 136 25.5.2012, p. 1): http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2012:136:0001:0040:en:PDF