Effects of Sucralose in Insulin Sensitivity

NCT04182464 | Completed

• 1 other identifier: 2635
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Recently, it has been proposed that the consumption of non-nutritive sweeteners, including sucralose, it's not harmless and is related with metabolic effects. Some studies have reported that sucralose produces alterations in glucose homeostasis. In vitro studies indicate that sucralose is capable of interacting with sweet taste receptors (T1R2 and T1R3) in the intestine, thus increasing the expression of glucose transporters including the sodium-glucose cotransporter type 1 (SGLT1) and the glucose transporter 2 (GLUT2), increasing glucose absorption. This interaction with intestinal sweet taste receptors also generates an increase in the secretion of the incretins glucagon-like peptide type 1 (GLP-1) and the glucose-dependent insulinotropic polypeptide (GIP), which might enhance the postprandial insulin release. However, these results are preliminary and it's desirable to confirm if sucralose consumption is associated with glucose metabolism modifications using an appropriate methodological design and with gold standard methods. The aim of this triple-blind, placebo-controlled, parallel, randomized clinical trial is to confirm the changes in insulin sensitivity associated with sucralose consumption in humans, to identify whether these changes are in the liver or skeletal muscle and to investigate the pathophysiological mechanisms generating these changes. Specifically, we will investigate if sucralose generates a dysbiosis in the gut microbiota that could be related to insulin resistance by increasing concentrations of lipopolysaccharide, a toxin present in Gram-negative bacteria that triggers a low grade inflammation known as metabolic endotoxemia. In addition, the changes in postprandial concentrations of GLP-1, glucose, insulin and C-peptide due to the combination of sucralose with a mixed meal will be investigated. The results of this study will determine if sucralose consumption, frequently used as a non-nutritive sweetener, is associated to significant changes in glucose homeostasis in humans.

Conditions

Insulin Sensitivity/Resistance

Keywords

sucralose; hyperinsulinemic-euglycemic clamp; insulin sensitivity

Outcome Measures

Primary Outcomes (2)

• Liver insulin sensitivity

  To evaluate changes in liver insulin sensitivity after sucralose consumption in comparison to placebo

  baseline and 30 days after the intervention

• Muscle insulin sensitivity

  To evaluate changes in skeletal muscle insulin sensitivity after sucralose consumption in comparison to placebo

  baseline and 30 days after the intervention

Study Arms (2)

Sucralose

EXPERIMENTAL

The intervention will consist of capsules filled with pure sucralose. Each capsule will contain 90 mg of sucralose. Participants will be asked to consume one capsule in each meal (three per day) in order to achieve an ingestion of 270 mg of sucralose, this quantity corresponds approximately to the 30% of the acceptable daily intake (ADI) of sucralose for a lean person. This was calculated based on the ADI established by the joint FAO/WHO expert committee on food additives (JECFA) of 15 mg per kg of body weight per day of sucralose.

Other: Sucralose

Placebo

PLACEBO COMPARATOR

The intervention will consist of capsules filled with placebo (cornstarch). Each capsule will contain 90 mg of cornstarch. Participants will be asked to consume one capsule in each meal (three per day) in order to achieve an ingestion of 270 mg of placebo, this quantity is in order to match the sucralose consumed in the intervention group.

Other: Placebo

Interventions

Sucralose OTHER

Food additive used to replace sugar providing a sweet taste without calories

Also known as: non-nutritive sweetener

Sucralose

Placebo OTHER

Cornstarch without significant physiological effects

Placebo

Eligibility Criteria

• Age: 20 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Normal BMI (18.5-24.9 kg/m2)
• Low habitual consumption of non-nutritive sweeteners (NNS
• Fasting plasma insulin concentration of \<12 mU/L

You may not qualify if:

• Diabetes or altered glucose metabolism (abnormal fasting glucose, glucose intolerance or elevated glycated hemoglobin)
• Use of antibiotics in the last 3 months
• Use of probiotics through pharmaceutical products
• Liver or kidney disease
• Use of medications that could interfere with insulin sensitivity
• Severe intestinal diseases
• History of bariatric surgery
• Pregnancy or lactation

Sponsors & Collaborators

• Paloma Almeda-Valdés: lead

Study Sites (1)

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Mexico City, 14080, Mexico

Location

Related Publications (5)

• Romo-Romo A, Aguilar-Salinas CA, Gomez-Diaz RA, Brito-Cordova GX, Gomez-Velasco DV, Lopez-Rocha MJ, Almeda-Valdes P. Non-Nutritive Sweeteners: Evidence on their Association with Metabolic Diseases and Potential Effects on Glucose Metabolism and Appetite. Rev Invest Clin. 2017 May-Jun;69(3):129-138. doi: 10.24875/ric.17002141.

  PMID: 28613282 BACKGROUND

• 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.

  PMID: 23633524 BACKGROUND

• 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

• Romo-Romo A, Aguilar-Salinas CA, Brito-Cordova GX, Gomez-Diaz RA, Almeda-Valdes P. Sucralose decreases insulin sensitivity in healthy subjects: a randomized controlled trial. Am J Clin Nutr. 2018 Sep 1;108(3):485-491. doi: 10.1093/ajcn/nqy152.

  PMID: 30535090 BACKGROUND

• Lertrit A, Srimachai S, Saetung S, Chanprasertyothin S, Chailurkit LO, Areevut C, Katekao P, Ongphiphadhanakul B, Sriphrapradang C. Effects of sucralose on insulin and glucagon-like peptide-1 secretion in healthy subjects: a randomized, double-blind, placebo-controlled trial. Nutrition. 2018 Nov;55-56:125-130. doi: 10.1016/j.nut.2018.04.001. Epub 2018 Apr 21.

  PMID: 30005329 BACKGROUND

MeSH Terms

Conditions

Insulin Resistance

Interventions

trichlorosucrose

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Paloma Almeda-Valdes, MD, PhD

  Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The use of identical capsules will allow the blinding, the capsules will be deposited in bottles numbered sequentially according to the enrollment process and neither the participants nor the researches will know the content of the capsules or the group assigned.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Staff physician

Model Details: Triple-blind, parallel, placebo-controlled, randomized clinical trial.

Study Record Dates

• First Submitted: November 26, 2019
• First Posted: December 2, 2019
• Study Start: November 1, 2019
• Primary Completion: August 30, 2021
• Study Completion: October 30, 2021
• Last Updated: October 19, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)