Effects of Sucralose in Gut Intestinal Microbiota and Postprandial GLP-1

NCT06094894 | Completed

• 1 other identifier: 2635.2
• Study Type: interventional
• Target: 40
• 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 can interact 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 found 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

GLP-1; Gut Microbiota; Insulin Resistance

Keywords

incretins; gut microbiota; sucralose; insulin resistance

Outcome Measures

Primary Outcomes (7)

• glucose

  To evaluate the changes in postprandial glucose concentrations during a mixed meal after sucralose consumption in comparison to placebo

  baseline and 30 days after the intervention

• insulin

  To evaluate the changes in postprandial insulin concentrations during a mixed meal after sucralose consumption in comparison to placebo

  baseline and 30 days after the intervention

• C-peptide

  To evaluate the changes in postprandial C-peptide concentrations during a mixed meal after sucralose consumption in comparison to placebo

  baseline and 30 days after the intervention

• GLP-1

  To evaluate the changes in postprandial GLP-1 area under the curve during a mixed meal after sucralose consumption in comparison to placebo

  baseline and 30 days after the intervention

• gut microbiota

  To compare the change in the relative abundance of colony forming units of bacterial genus and species after sucralose consumption in comparison to placebo through messenger RNA sequencing

  baseline and 30 days after the intervention

• PYY

  To evaluate the changes in postprandial PYY area under the curve during a mixed meal after sucralose consumption in comparison to placebo

  baseline and 30 days after the intervention

• ghrelin

  To evaluate the changes in postprandial ghrelin area under the curve during a mixed meal after sucralose consumption in comparison to placebo

  baseline and 30 days after the intervention

Secondary Outcomes (4)

• lipopolysaccharide

  baseline and 30 days after the intervention

• C-reactive protein

  baseline and 30 days after the intervention

• IL-6

  baseline and 30 days after the intervention

• tumor necrosis factor-alpha

  baseline and 30 days after the intervention

Other Outcomes (4)

• fecal short chain fatty acids

  baseline and 30 days after the intervention

• serum fatty acid profile

  baseline and 30 days after the intervention

• Curli protein fecal expression

  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) 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

• Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran: lead

Study Sites (1)

Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán

Mexico City, Mexico City, 14080, Mexico

Location

Related Publications (9)

• 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

• 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

• 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

• Dalenberg JR, Patel BP, Denis R, Veldhuizen MG, Nakamura Y, Vinke PC, Luquet S, Small DM. Short-Term Consumption of Sucralose with, but Not without, Carbohydrate Impairs Neural and Metabolic Sensitivity to Sugar in Humans. Cell Metab. 2020 Mar 3;31(3):493-502.e7. doi: 10.1016/j.cmet.2020.01.014.

  PMID: 32130881 BACKGROUND

• Suez J, Cohen Y, Valdes-Mas R, Mor U, Dori-Bachash M, Federici S, Zmora N, Leshem A, Heinemann M, Linevsky R, Zur M, Ben-Zeev Brik R, Bukimer A, Eliyahu-Miller S, Metz A, Fischbein R, Sharov O, Malitsky S, Itkin M, Stettner N, Harmelin A, Shapiro H, Stein-Thoeringer CK, Segal E, Elinav E. Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance. Cell. 2022 Sep 1;185(18):3307-3328.e19. doi: 10.1016/j.cell.2022.07.016. Epub 2022 Aug 19.

  PMID: 35987213 BACKGROUND

• Bueno-Hernandez N, Esquivel-Velazquez M, Alcantara-Suarez R, Gomez-Arauz AY, Espinosa-Flores AJ, de Leon-Barrera KL, Mendoza-Martinez VM, Sanchez Medina GA, Leon-Hernandez M, Ruiz-Barranco A, Escobedo G, Melendez G. Chronic sucralose consumption induces elevation of serum insulin in young healthy adults: a randomized, double blind, controlled trial. Nutr J. 2020 Apr 13;19(1):32. doi: 10.1186/s12937-020-00549-5.

  PMID: 32284053 BACKGROUND

• Romo-Romo A, Sanchez-Tapia M, Lopez-Carrasco MG, Guillen-Pineda LE, Brito-Cordova GX, Martagon AJ, Granados-Portillo O, Walther G, Gomez-Perez FJ, Aguilar-Salinas CA, Tovar AR, Torres N, Almeda-Valdes P. Sucralose consumption modifies glucose homeostasis, gut microbiota, Curli protein, and related metabolites in healthy individuals: A randomized placebo-controlled, triple-blind trial. Clin Nutr ESPEN. 2025 Oct;69:733-744. doi: 10.1016/j.clnesp.2025.08.029. Epub 2025 Sep 2.

  PMID: 40907790 DERIVED

MeSH Terms

Conditions

Insulin Resistance

Interventions

trichlorosucrose

Condition Hierarchy (Ancestors)

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

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 researchers will know the content of the capsules, or the group assigned.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

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

Study Record Dates

• First Submitted: October 17, 2023
• First Posted: October 23, 2023
• Study Start: June 1, 2023
• Primary Completion: February 29, 2024
• Study Completion: March 1, 2024
• Last Updated: April 4, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)