Effects of Low/No Calorie Sweeteners on Glucose Tolerance

Glucose Tolerance Clinical Trial

Official title:

The Effect of Regular Consumption of Low/No Calorie Sweeteners on Glycemic Response and Glucagon Like Peptide-1 Secretion in Healthy Adults: A Randomized Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04904133
• Other study ID #: 28850
• Secondary ID: 218S378
• Status: Completed
• Phase: N/A
• Start date: April 2, 2019
• Est. completion date: July 2, 2019

Study information

• Verified date: May 2021
• Source: Acibadem University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Description:

Excessive sugar consumption has been related to chronic metabolic problems, including obesity, type 2 diabetes, neuroinflammatory diseases, etc. Therefore, it is recommended to decrease added sugar intake below 10% of total energy intake. Low/no calorie sweeteners (LNCS) may seem as a good alternative to added sugars because they provide sweetness without adding calories to the diet. Although they may reduce energy intake and prevent weight gain, studies investigating the short and long term effects of these sweeteners on metabolic profile are controversial. Therefore, there is a need for future studies to shed light on metabolic effects of these compounds in humans.

Some observational and clinical studies show that they may cause insulin resistance and type 2 diabetes. There are possible mechanisms that may explain this relationship. One of these possible mechanisms is interaction with sweet taste receptors (STRs). It has been shown that STRs not only found in oral cavity but also in extra-oral tissues, such as gastrointestinal tract, pancreas, brain, etc. In vitro studies with sucralose, it has been shown that it may activate STRs in L-cells and stimulate GLP-1 release in a similar manner with glucose. However, these results were not confirmed in vivo.

There are at least six different LNCS approved for human use worldwide. However, each of them have different biological fate in terms of absorption, metabolism and excretion characteristics in the body. Therefore, result of a study with one of LNCS cannot be extrapolated for all LNCS; each of them should be studied in well-designed studies.

In this study it is hypothesized that LNCS may activate STRs in intestinal L-cells and alter release of GLP-1; as a result impair glucose tolerance. In acute human studies, these effects are tested and there are controversial results in regard to glucose tolerance or incretin release. However, individuals who want to consume fewer calories or to better control their blood glucose use LNCS in place of sugar for longer period of time. For this reason, we wanted to test the effects of regular use of LNCS on glucose tolerance and incretin release.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: July 2, 2019
• Est. primary completion date: May 12, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 19 Years to 45 Years

Eligibility

Inclusion Criteria:

• Healthy,

• Normoglycemic,

• Female,

• 19-45 years old,

• Weight-stable past 3 months

Exclusion Criteria:

• 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)

Related Conditions & MeSH terms

• Glucose Tolerance
• Healthy Population

Intervention

Other:
• Low/No Calorie Sweeteners
LNCS powdered and then dissolved in water.
• Placebo Group
Water

Locations

Country	Name	City	State
Turkey	Acibadem Dr. Sinasi Can (Kadiköy) Hospital	Istanbul	Anadolu

Sponsors (1)

Lead Sponsor	Collaborator
Acibadem University

Country where clinical trial is conducted

Turkey, 

References & Publications (12)

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. Review. — View Citation

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. — View Citation

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. Epub 2007 Aug 27. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

Romo-Romo A, Aguilar-Salinas CA, Brito-Córdova GX, Gómez Díaz RA, Vilchis Valentín 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. Review. — View Citation

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. — View Citation

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. eCollection 2016. — View Citation

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. — View Citation

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 Jan 2;364:k4718. doi: 10.1136/bmj.k4718. Erratum in: BMJ. 2019 Jan 15;364:l156. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Glucagon-like peptide-1 (GLP-1) release	Change from baseline fasting GLP-1 levels at 4 weeks observed.	Week 4
Secondary	Body Weight	Change from baseline body weight at 4 weeks observed. Participants were weighed on a digital scale (Tanita MC 180) in fasted state. Weights were expressed in kilograms (kg).	Week 4
Secondary	Fat Mass	Change from baseline fat mass (kg) at 4 weeks observed. Fat mass was determined by bioelectrical impedance analysis (BIA) method (Tanita MC180).	Week 4
Secondary	Fat-Free Mass	Change from baseline fat-free mass (kg) at 4 weeks observed. Fat-free mass was determined by bioelectrical impedance analysis (BIA) method (Tanita MC180).	Week 4
Secondary	Total Body Water	Change from baseline total body water (kg) at 4 weeks observed. Total body water was determined by bioelectrical impedance analysis (BIA) method (Tanita MC180).	Week 4
Secondary	Body Mass Index (BMI)	Change from baseline BMI at 4 weeks observed. BMI was calculated as weight (in kilograms) divided by the square of height (in meters).	Week 4
Secondary	Waist Circumference	Change from baseline waist circumference (in centimeters) at 4 weeks observed.	Week 4