Metabolic Effects of Non-nutritive Sweeteners (NNS)

The purpose of this research study is to examine whether sugar-replacement sweeteners that are currently on the market (ex. Sucralose, which is in Splenda) change how well the body works to control blood sugar.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Dietary supplement: Sucralose; Dietary supplement: glucose load; Other: Water

Detailed Description

The investigators of this study have recently found that sucralose, the most commonly used non-nutritive sweetener (NNS), affects the glycemic response to an oral glucose tolerance test (OGTT) and potentiates glucose-stimulated insulin secretion in obese people who are not regular consumers of NNS. However, studies conducted in healthy lean adults, none of which control for previous use of NNS, show that sucralose does not affect glycemic or hormonal responses to the ingestion of glucose or other carbohydrates. Therefore, we do not know a) whether sucralose effects are limited to obese subjects, or are generalizable to lean people when controlling for prior history of NNS consumption, and b) mechanism(s) responsible for the acute effect of sucralose on glucose metabolism as we measured in obese subjects. The aim of this study is to determine the effects of an acute intake of sucralose on the metabolic response to an oral glucose tolerance test in lean and obese people.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Urbana, Illinois, United States, 61801
      • University of Illinois at Urbana Champaign

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• BMI ≥ 30 kg/m2 or BMI ≥ 18 kg/m2 and BMI<25 kg/m2
• "insulin sensitive": based on the homeostasis model assessment of insulin resistance (HOMA-IR) <3

Exclusion Criteria:

• BMI ≥ 25 kg/m2 and BMI<30 kg/m2
• HOMA-IR>3
• Current smoker or quit smoking less than 6 months ago
• pregnancy or breastfeeding
• subjects who have malabsorptive syndromes, phenylketonuria, inflammatory intestinal disease, liver or kidney diseases, diabetes
• subjects who are taking any medication that might affect metabolism
• anemia
• regular use of non-nutritive sweeteners

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Drink Sucralose; Subjects will drink sucralose 10 min before drinking a glucose load	Dietary supplement: Sucralose; 60 ml of 2mM sucralose; Dietary supplement: glucose load
Placebo Comparator: Drink Water; Subjects will drink water 10 min before drinking a glucose load	Dietary supplement: glucose load; Other: Water; 60 ml of water
Experimental: Taste and spit Sucralose; Subjects will taste and spit up sucralose 10 min before drinking a glucose load	Dietary supplement: Sucralose; 60 ml of 2mM sucralose; Dietary supplement: glucose load

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak insulin secretion rate	Blood samples will be collected before and for 5 hours after drinking a glucose load to determine plasma insulin and C-peptide. Insulin secretion rate will be assessed using the minimal model of Breda and collaborators.	up to 5 hours after drinking a glucose load
Glucose rate of appearance	Blood samples will be collected before and for 5 hours after drinking a glucose load to determine glucose and glucose tracer:tracee ratios.	up to 5 hours after drinking a glucose load

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glucose-dependent insulinotropic polypeptide (GIP)	Blood samples will be collected before and for 5 hours after drinking a glucose load to determine GIP.	up to 5 hours after drinking a glucose load
Sucralose concentrations in plasma	Sucralose concentrations in plasma will be measured by using liquid chromatography-mass spectrometry.	up to 310 min after drinking the sucralose load

Collaborators and Investigators

• Sponsor: University of Illinois at Urbana-Champaign
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Marta Y Pepino, PhD, University of Illinois at Urbana-Champaign

Publications and helpful links

General Publications

• 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.
• Swithers SE. Artificial sweeteners produce the counterintuitive effect of inducing metabolic derangements. Trends Endocrinol Metab. 2013 Sep;24(9):431-41. doi: 10.1016/j.tem.2013.05.005. Epub 2013 Jul 10.
• Pepino MY, Tiemann CD, Patterson BW, Wice BM, Klein S. Sucralose affects glycemic and hormonal responses to an oral glucose load. Diabetes Care. 2013 Sep;36(9):2530-5. doi: 10.2337/dc12-2221. Epub 2013 Apr 30.
• Margolskee RF, Dyer J, Kokrashvili Z, Salmon KS, Ilegems E, Daly K, Maillet EL, Ninomiya Y, Mosinger B, Shirazi-Beechey SP. T1R3 and gustducin in gut sense sugars to regulate expression of Na+-glucose cotransporter 1. Proc Natl Acad Sci U S A. 2007 Sep 18;104(38):15075-80. doi: 10.1073/pnas.0706678104. Epub 2007 Aug 27.
• Brown RJ, de Banate MA, Rother KI. Artificial sweeteners: a systematic review of metabolic effects in youth. Int J Pediatr Obes. 2010 Aug;5(4):305-12. doi: 10.3109/17477160903497027.

Study record dates

Study Major Dates

• Study Start: April 1, 2015
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): July 1, 2017

Study Registration Dates

• First Submitted: April 6, 2015
• First Submitted That Met QC Criteria: April 8, 2015
• First Posted (Estimate): April 9, 2015

Study Record Updates

• Last Update Posted (Actual): September 21, 2017
• Last Update Submitted That Met QC Criteria: September 19, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: sucralose
• Other Study ID Numbers: 201412080; P30DK020579 (U.S. NIH Grant/Contract)