Effects of Low/No Calorie Sweeteners on Glucose Tolerance

NCT04904133 | Completed

• 2 other identifiers: 28850218S378
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to determine the effects of chronic exposure to some low/no calorie sweeteners (LNCS) on glucose tolerance and glucagon like peptide 1 (GLP-1) release in healthy individuals. LNCS examined in this study are saccharin, sucralose and aspartame+acesulfame-K. The amounts of LNCS given to the participants are kept similar to daily life exposure; far less than the Acceptable Daily Intakes (ADIs) levels proposed by Food and Drug Administration (FDA) or European Food Safety Authority (EFSA).

Conditions

Healthy Population; Glucose Tolerance

Keywords

artificial sweeteners; non-nutritive sweeteners; oral glucose tolerance; glucagon-like peptide-1; insulin secretion; satiety peptides

Outcome Measures

Primary Outcomes (3)

• 3 Hours Plasma Glucose

  Change from baseline plasma glucose levels at 4 weeks observed. Participants underwent a 3-h oral glucose tolerance test (3-h OGTT) by consuming a 250 mL 75 g glucose solution, and blood samples were collected at 60, 120, 180 min.

  3 hours

• 3 Hours Plasma Insulin

  Change from baseline insulin levels at 4 weeks observed. Participants underwent a 3-h oral glucose tolerance test (3-h OGTT) by consuming a 250 mL 75 g glucose solution, and blood samples were collected at 60, 120, 180 min.

  3 hours

• Glucagon-like peptide-1 (GLP-1) release

  Change from baseline fasting GLP-1 levels at 4 weeks observed.

  Week 4

Secondary Outcomes (6)

• Body Weight

  Week 4

• Fat Mass

  Week 4

• Fat-Free Mass

  Week 4

• Total Body Water

  Week 4

• Body Mass Index (BMI)

  Week 4

Study Arms (4)

Saccharine Group

ACTIVE COMPARATOR

140 mg saccharin (Hermesetas) dissolved in 330 mL water for 4 weeks.

Other: Low/No Calorie Sweeteners

Sucralose Group

ACTIVE COMPARATOR

66 mg sucralose (Splenda) dissolved in 330 mL water for 4 weeks.

Other: Low/No Calorie Sweeteners

Aspartame+Acesulfame-K Group

ACTIVE COMPARATOR

88 mg aspartame+88 mg acesulfame-K (Takita) dissolved in 330 mL water for 4 weeks.

Other: Low/No Calorie Sweeteners

Control Group

PLACEBO COMPARATOR

330 mL water for 4 weeks.

Other: Placebo Group

Interventions

Low/No Calorie Sweeteners OTHER

LNCS powdered and then dissolved in water.

Aspartame+Acesulfame-K Group; Saccharine Group; Sucralose Group

Placebo Group OTHER

Water

Also known as: Control

Control Group

Eligibility Criteria

• Age: 19 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy,
• Normoglycemic,
• Female,
• years old,
• Weight-stable past 3 months

You may not qualify if:

• Insulin resistance,
• Type 2 diabetes mellitus,
• Presence of acute/chronic infection,
• Use of medication that may affect glucose metabolism (thiazide diuretics, glucocorticoids, estrogen or beta blockers)
• Chronic alcohol intake,
• Regular consumption of diet soda (more than one can of soda per week)

Sponsors & Collaborators

• Acibadem University: lead

Study Sites (1)

Acıbadem Dr. Şinasi Can (Kadıköy) Hospital

Istanbul, Anadolu, 34718, Turkey (Türkiye)

Location

Related Publications (13)

• Suez J, Korem T, Zeevi D, Zilberman-Schapira G, Thaiss CA, Maza O, Israeli D, Zmora N, Gilad S, Weinberger A, Kuperman Y, Harmelin A, Kolodkin-Gal I, Shapiro H, Halpern Z, Segal E, Elinav E. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature. 2014 Oct 9;514(7521):181-6. doi: 10.1038/nature13793. Epub 2014 Sep 17.

  PMID: 25231862 BACKGROUND

• Rogers PJ, Hogenkamp PS, de Graaf C, Higgs S, Lluch A, Ness AR, Penfold C, Perry R, Putz P, Yeomans MR, Mela DJ. 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 Mar;40(3):381-94. doi: 10.1038/ijo.2015.177. Epub 2015 Sep 14.

  PMID: 26365102 BACKGROUND

• 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 Sep;100(3):765-77. doi: 10.3945/ajcn.113.082826. Epub 2014 Jun 18.

  PMID: 24944060 BACKGROUND

• Toews I, Lohner S, Kullenberg 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 Jan 2;364:k4718. doi: 10.1136/bmj.k4718.

  PMID: 30602577 BACKGROUND

• Romo-Romo A, Aguilar-Salinas CA, Brito-Cordova GX, Gomez Diaz RA, Vilchis Valentin D, Almeda-Valdes P. Effects of the Non-Nutritive Sweeteners on Glucose Metabolism and Appetite Regulating Hormones: Systematic Review of Observational Prospective Studies and Clinical Trials. PLoS One. 2016 Aug 18;11(8):e0161264. doi: 10.1371/journal.pone.0161264. eCollection 2016.

  PMID: 27537496 BACKGROUND

• Jang HJ, Kokrashvili Z, Theodorakis MJ, Carlson OD, Kim BJ, Zhou J, Kim HH, Xu X, Chan SL, Juhaszova M, Bernier M, Mosinger B, Margolskee RF, Egan JM. Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1. Proc Natl Acad Sci U S A. 2007 Sep 18;104(38):15069-74. doi: 10.1073/pnas.0706890104. Epub 2007 Aug 27.

  PMID: 17724330 BACKGROUND

• Brown RJ, Rother KI. Non-nutritive sweeteners and their role in the gastrointestinal tract. J Clin Endocrinol Metab. 2012 Aug;97(8):2597-605. doi: 10.1210/jc.2012-1475. Epub 2012 Jun 7.

  PMID: 22679063 BACKGROUND

• 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 beta-cells activates the calcium and cyclic AMP signaling systems and stimulates insulin secretion. PLoS One. 2009;4(4):e5106. doi: 10.1371/journal.pone.0005106. Epub 2009 Apr 8.

  PMID: 19352508 BACKGROUND

• 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 Mar;296(3):E473-9. doi: 10.1152/ajpendo.90636.2008. Epub 2008 Dec 23.

  PMID: 19106249 BACKGROUND

• Sylvetsky AC, Brown RJ, Blau JE, Walter M, Rother KI. Hormonal responses to non-nutritive sweeteners in water and diet soda. Nutr Metab (Lond). 2016 Oct 21;13:71. doi: 10.1186/s12986-016-0129-3. eCollection 2016.

  PMID: 27777606 BACKGROUND

• Ma J, Bellon M, Wishart JM, Young R, Blackshaw LA, Jones KL, Horowitz M, Rayner CK. Effect of the artificial sweetener, sucralose, on gastric emptying and incretin hormone release in healthy subjects. Am J Physiol Gastrointest Liver Physiol. 2009 Apr;296(4):G735-9. doi: 10.1152/ajpgi.90708.2008. Epub 2009 Feb 12.

  PMID: 19221011 BACKGROUND

• Temizkan S, Deyneli O, Yasar M, Arpa M, Gunes M, Yazici D, Sirikci O, Haklar G, Imeryuz N, Yavuz DG. 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 Feb;69(2):162-6. doi: 10.1038/ejcn.2014.208. Epub 2014 Oct 1.

  PMID: 25271009 BACKGROUND

• Orku SE, Suyen G, Bas M. The effect of regular consumption of four low- or no-calorie sweeteners on glycemic response in healthy women: A randomized controlled trial. Nutrition. 2023 Feb;106:111885. doi: 10.1016/j.nut.2022.111885. Epub 2022 Nov 1.

  PMID: 36470113 DERIVED

Study Officials

• Saziye E Orku, Dr.

  Acibadem University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Participants were not informed about the study group and also which sweetener they consumed.
• Purpose: SCREENING
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Ph.D, Department of Nutrition and Dietetics, Acıbadem University

Model Details: Volunteers were randomly divided into 4 groups (saccharin, sucralose, aspartame+acesulfame-K \[Asp+Ace-K\], control) and asked to drink the LNCS sweetened water once a day for 4-wks. All study groups and concentration of LNCS they consumed written as follows; Saccharin group: 330 mL water + 140 mg saccharine Sucralose group: 330 mL water + 66 mg sucralose Asp+Ace-K group: 330 mL water + 88 mg aspartame and 88 mg acesulfame-K Control group IV: 330 mL water only

Study Record Dates

• First Submitted: May 14, 2021
• First Posted: May 27, 2021
• Study Start: April 2, 2019
• Primary Completion: May 12, 2019
• Study Completion: July 2, 2019
• Last Updated: May 27, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)