Chronic sucralose consumption induces elevation of serum insulin in young healthy adults: a randomized, double blind, controlled trial

Nallely Bueno-Hernández, Marcela Esquivel-Velázquez, Raúl Alcántara-Suárez, Angélica Y Gómez-Arauz, Aranza J Espinosa-Flores, Karen L de León-Barrera, Viridiana M Mendoza-Martínez, Gabriela A Sánchez Medina, Mireya León-Hernández, Alejandra Ruiz-Barranco, Galileo Escobedo, Guillermo Meléndez, Nallely Bueno-Hernández, Marcela Esquivel-Velázquez, Raúl Alcántara-Suárez, Angélica Y Gómez-Arauz, Aranza J Espinosa-Flores, Karen L de León-Barrera, Viridiana M Mendoza-Martínez, Gabriela A Sánchez Medina, Mireya León-Hernández, Alejandra Ruiz-Barranco, Galileo Escobedo, Guillermo Meléndez

Abstract

Background: Non-nutritive sweeteners (NNS) are widely consumed by humans due to their apparent innocuity, especially sucralose. However, several studies link sucralose consumption to weight gain and metabolic derangements, although data are still contradictory.

Objective: To determine the effect of acute and chronic consumption of sucralose on insulin and glucose profiles in young healthy adults.

Material and methods: This was a randomized, parallel, double-blind, placebo-controlled trial conducted in healthy young adults from 18 to 35 years old, without insulin resistance. A hundred thirty seven participants were randomized into three groups: a) volunteers receiving 48 mg sucralose, b) volunteers receiving 96 mg sucralose, and c) controls receiving water as placebo. All participants underwent a 3-h oral glucose tolerance test (OGTT) preceded by consuming sucralose or placebo 15 min before glucose load, at two time points: week zero (Wk0) and week ten (Wk10). Serum insulin and glucose were measured every 15 min during both OGTTs.

Results: Compared to Wk0, consumption of sucralose for 10 weeks provoked 1) increased insulin concentrations at 0 min (7.5 ± 3.4 vs 8.8 ± 4.1 μIU/mL; p = 0.01), 30 min (91.3 ± 56.2 vs 110.1 ± 49.4 μIU/mL; p = 0.05), 105 min (47.7 ± 24.4 vs 64.3 ± 48.2 μIU/mL; p = 0.04) and 120 min (44.8 ± 22.1 vs 63.1 ± 47.8 μIU/mL; p = 0.01) in the 48 mg sucralose group; 2) increased blood glucose at - 15 min (87.9 ± 4.6 vs 91.4 ± 5.4 mg/dL; p = 0.003), 0 min (88.7 ± 4 vs 91.3 ± 6 mg/dL; p = 0.04) and 120 min (95.2 ± 23.7 vs 106.9 ± 19.5 mg/dL; p = 0.009) in the 48 mg sucralose group; 3) increased area under the curve (AUC) of insulin in both 48 and 96 mg sucralose groups (9262 vs 11,398; p = 0.02 and 6962 vs 8394; p = 0.12, respectively); and 4) reduced Matsuda index in the 48 mg sucralose group (6.04 ± 3.19 vs 4.86 ± 2.13; p = 0.01).

Conclusions: These data show that chronic consumption of sucralose can affect insulin and glucose responses in non-insulin resistant healthy young adults with normal body mass index (between 18.5 and 24.9 kg/m2), however, the effects are not consistent with dose; further research is required.

Clinical trial registry: NCT03703141.

Keywords: Glucose; Insulin; Non-nutritive sweeteners; Placebo-controlled trial; Sucralose.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flow chart of the study. The flow diagram shows the progress of the participants who were recruited, randomized and followed up throughout the study, according to the CONSORT (Consolidated Standards of Reporting Trials) guidelines
Fig. 2
Fig. 2
OGTT insulin concentration values of the participants. Wk0 and Wk10 OGTT insulin curves are depicted for a) control group, b) 48 mg sucralose group and c) 96 mg sucralose group. d) Mean insulin AUC compared between Wk0 and Wk10 OGTTs for each group. Arrows indicate the time in which sucralose or water (placebo) were administered, as well as the glucose load. Data are mean ± SEM. *p < 0.05. Statistical analysis: Two-tailed t-tests and two-tailed paired-t tests
Fig. 3
Fig. 3
OGTT glucose concentration values of the participants. Wk0 and Wk10 OGTT glucose curves are depicted for a) control, b) 48 mg sucralose and c) 96 mg sucralose. d) Mean glucose AUC compared between Wk0 and Wk10 OGTTs for each group. Arrows indicate the time in which sucralose or water (placebo) were administered, as well as the glucose load. Data are mean ± SEM. *p < 0.05. Statistical analysis: two-tailed paired-t tests
Fig. 4
Fig. 4
Analysis of Wk0 and Wk10 glucose and insulin AUC between the sucralose exposed group (48 mg & 96 mg groups) and not exposed group (control). Data are mean ± SEM. *p 

References

    1. World Obesity Federation. Global Obesity Observatory | Obesity prevalence worldwide - Adults. Available from: . [cited 2019 Apr 29].
    1. Rippe JM, Angelopoulos TJ. Relationship between Added Sugars Consumption and Chronic Disease Risk Factors: Current Understanding. Nutrients. 2016;8(11).
    1. Shankar P, Ahuja S, Sriram K. Non-nutritive sweeteners: review and update. Nutrition. 2013;29:1293–1299. doi: 10.1016/j.nut.2013.03.024.
    1. Sylvetsky AC, Rother KI. Trends in the consumption of low-calorie sweeteners. Physiol Behav. 2016;164:446–450. doi: 10.1016/j.physbeh.2016.03.030.
    1. Erythropel HC, Kong G, deWinter TM, O’Malley SS, Jordt SE, Anastas PT, et al. Presence of High-Intensity Sweeteners in Popular Cigarillos of Varying Flavor Profiles. JAMA. 2018;320:1380. doi: 10.1001/jama.2018.11187.
    1. WHO, FAO, COMISSION CAC. REPORT OF THE 50th SESSION OF THE CODEX COMMITTEE ON FOOD ADDITIVES. 2018. Available from: . [cited 2019 Apr 29].
    1. Chattopadhyay S, Raychaudhuri U, Chakraborty R. Artificial sweeteners - a review. J Food Sci Technol Springer. 2014;51:611–621. doi: 10.1007/s13197-011-0571-1.
    1. Food and Drug Administration. High-Intensity Sweeteners. Available from: . [cited 2019 Aug 26].
    1. Sylvetsky AC. Metabolic effects of low-calorie sweeteners: a brief review. Obesity. 2018;26:S25–S31. doi: 10.1002/oby.22156.
    1. Pepino MY, Tiemann CD, Patterson BW, Wice BM, Klein S. Sucralose affects glycemic and hormonal responses to an oral glucose load. Diabetes Care. 2013;36:2530–2535. doi: 10.2337/dc12-2221.
    1. Suez J, Korem T, Zeevi D, Zilberman-schapira G, Thaiss CA, Maza O, et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature. 2014;514:181–186. doi: 10.1038/nature13793.
    1. Nettleton JE, Reimer RA, Shearer J. Reshaping the gut microbiota: Impact of low calorie sweeteners and the link to insulin resistance? Physiol Behav. 2016;164:488–493. doi: 10.1016/j.physbeh.2016.04.029.
    1. Daly K, Darby AC, Shirazi-Beechey SP. Low calorie sweeteners and gut microbiota. Physiol Behav. 2016;164:494–500. doi: 10.1016/j.physbeh.2016.03.014.
    1. Goza R, Bunout D, Barrera G, de la Maza M, Hirsch S. Effect of acute consumption of artificially sweetened beverages on blood glucose and insulin in healthy subjects. J Nutr Food Sci. 2018;08:1–5.
    1. Grotz VL, Pi-Sunyer X, Porte D, Roberts A, Richard TJ. A 12-week randomized clinical trial investigating the potential for sucralose to affect glucose homeostasis. Regul Toxicol Pharmacol. 2017;88:22–33. doi: 10.1016/j.yrtph.2017.05.011.
    1. Brown AW, Bohan Brown MM, Onken KL, Beitz DC. 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. 2015;31:882–888. doi: 10.1016/j.nutres.2011.10.004.
    1. 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;181:100–109. doi: 10.1016/j.physbeh.2017.09.009.
    1. Greenfield JR, Chisholm DJ. How sweet it is: Intestinal sweet taste receptors in type 2 diabetes. Diabetes. 2013;62(10):3336–7.
    1. Moher D, Hopewell S, Schulz KF, Montori V, Gøtzsche PC, Devereaux PJ, et al. CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials. J Clin Epidemiol Pergamon. 2010;63:e1–37. doi: 10.1016/j.jclinepi.2010.03.004.
    1. Qu HQ, Li Q, Rentfro AR, Fisher-Hoch SP, McCormick JB. The definition of insulin resistance using HOMA-IR for Americans of Mexican descent using machine learning. PLoS One. 2011;6:e21041. doi: 10.1371/journal.pone.0021041.
    1. Faul F, Erdfelder E, Lang A-G, Buchner A. G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007;39(2):175–91.
    1. Bueno-Henández N, Alcántara-Suárez R, Pérez-Castañeda M, Hernández León YA, Ruíz-Barranco AL, Escobedo G, et al. Content Validity and Reliability of a Food Frequency Questionnaire with Intense Sweeteners (FFQIS) in a Hispanic Population. enviado a publicación. J Nutr Food Sci. 2018;8(4):716.
    1. Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care. 1999;22:1462–1470. doi: 10.2337/diacare.22.9.1462.
    1. Grotz VL, Jokinen JD. Comment on Pepino et al. Sucralose affects glycemic and hormonal responses to an oral glucose load. Diabetes care. 2013;36:2530–2535. doi: 10.2337/dc12-2221.
    1. Sylvetsky AC, Brown RJ, Blau JE, Walter M, Rother KI. Hormonal responses to non-nutritive sweeteners in water and diet soda. Nutr Metab. 2016;13:71. doi: 10.1186/s12986-016-0129-3.
    1. Lertrit A, Srimachai S, Saetung S, Chanprasertyothin S, Chailurkit L or, 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. Nutrition 2018;55–56:125–130.
    1. Brown RJ, Rother KI. Non-nutritive sweeteners and their role in the gastrointestinal tract. J Clin Endocrinol Metab Narnia. 2012;97:2597–2605. doi: 10.1210/jc.2012-1475.
    1. Davis JN, Asigbee FM, Markowitz AK, Landry MJ, Vandyousefi S, Khazaee E, et al. Consumption of artificial sweetened beverages associated with adiposity and increasing HbA1c in Hispanic youth. Clin Obes. 2018;8:236. doi: 10.1111/cob.12260.
    1. Wang QP, Lin YQ, Zhang L, Wilson YA, Oyston LJ, Cotterell J, et al. Sucralose Promotes Food Intake through NPY and a Neuronal Fasting Response. Cell Metab. 2016;24:75–90. doi: 10.1016/j.cmet.2016.06.010.
    1. Kojima I, Nakagawa Y, Hamano K, Medina J, Li L, Nagasawa M. Glucose-Sensing Receptor T1R3: A New Signaling Receptor Activated by Glucose in Pancreatic β-Cells. Biol Pharm Bull. 2015;38:674–679. doi: 10.1248/bpb.b14-00895.
    1. Kojima I, Nakagawa Y, Ohtsu Y, Hamano K, Medina J, Nagasawa M. Return of the glucoreceptor: glucose activates the glucose-sensing receptor T1R3 and facilitates metabolism in pancreatic β-cells. J Diabetes Investig. 2015;6:256–263. doi: 10.1111/jdi.12304.
    1. Pepino MY. Metabolic effects of non-nutritive sweeteners. Physiol Behav. 2015;152:450–455. doi: 10.1016/j.physbeh.2015.06.024.
    1. Jang HJ, Kokrashvili Z, Theodorakis MJ, Carlson OD, Kim BJ, Zhou J, et al. Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1. Proc Natl Acad Sci U S A. 2007;104:15069–15074. doi: 10.1073/pnas.0706890104.
    1. Roberts A, Renwick AG, Sims J, Snodin DJ. Sucralose metabolism and pharmacokinetics in man. Food Chem Toxicol. 2000;38:31–41. doi: 10.1016/S0278-6915(00)00026-0.
    1. Wiebe N, Padwal R, Field C, Marks S, Jacobs R, Tonelli M. A systematic review on the effect of sweeteners on glycemic response and clinically relevant outcomes. BMC Med. 2011/11/19. Department of Medicine, 13–103 Clinical Sciences Building, University of Alberta, Edmonton, Alberta, T6G 2G3 Canada.: BioMed Central; 2011;9:123.
    1. Sylvetsky AC, Jin Y, Mathieu K, DiPietro L, Rother KI, Talegawkar SA. Low-calorie sweeteners: disturbing the energy balance equation in adolescents? Obesity. 2017;25:2049–2054. doi: 10.1002/oby.22005.

Source: PubMed

3
Iratkozz fel