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

March 8, 2024 updated by: Paloma Almeda-Valdés, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Changes in Gut Microbiota and Postprandial GLP-1 Concentration Due to Sucralose Consumption

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Study design:

This is a triple-blind, parallel, placebo-controlled, randomized clinical trial.

Sample size:

The sample size was calculated to observe a difference of 25% in GLP-1 area under the curve.

The calculation was done considering a probability of type I error (α) of 5%, with a power of 80% and adding an extra 20% for potential losses at follow-up.

The estimated sample size for the study is 40 subjects, 20 per group.

Randomization:

The participants will be randomly assigned to one of the two groups (sucralose or placebo) using the website Randomization.com (http://www.randomization.com) with a balanced block design of 5 blocks with 8 subjects each. The random allocation sequence will be done by an external researcher.

Intervention:

The intervention will consist of capsules filled with pure sucralose or placebo (cornstarch) accordingly to the group assignment. Each capsule will contain 90 mg of sucralose or placebo. 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 or placebo, 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 Food and Agriculture Organization of the United Nations (FAO)/World Health Organization (WHO) expert committee on food additives (JECFA) of 15 mg per kg of body weight per day of sucralose.

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.

Visit 1

An oral glucose tolerance test (OGTT) will be performed to confirm that participants do not have diabetes or prediabetes. Fasting insulin, lipid profile and glycated hemoglobin will be measured. Also, anthropometry (weight, height, waist, and hip circumference), blood pressure and heart rate will be documented. Body composition will be evaluated with dual X-ray absorptiometry (DXA) already available in the Research Unit and bioelectrical impedance. Physical activity will be registered with the questionnaire from the University of Laval that measure energy expenditure in Kcal per day. A format for three-day food intake record will be given to be prospectively registered by participants.

Visit 2

The three-day food record will be requested and reviewed to evaluate food consumption habits. A mixed meal tolerance test will be performed over two hours. The meal will consist of 523 kcal (49% carbohydrates, 17% protein, 34% lipids). Blood samples will be collected at 0, 30, 60, 90 and 120 minutes to measure glucose, insulin and glucagon-like peptide type 1 (GLP-1) concentrations. Also, lipopolysaccharide (LPS), C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-α) concentrations will be measured at the basal time. Ten minutes before the test participants will consume a capsule containing either sucralose or placebo (120 mg).

Participants will proportionate the first stool sample to evaluate gut microbiota.

The researchers will proportionate the bottle with capsules that each participant will consume during the intervention period (30 ± 2 days) in this visit. Also, each participant will be asked to record on the adherence format if they consumed the capsule at breakfast, lunch, and dinner each day of the intervention period and to record any symptom related to capsules ingestion. Another format to record three-day food consumption again will be given.

Visit 3

Participants will proportionate the second stool sample to evaluate changes in gut microbiota. Also, the physical activity questionnaire will be applied again, and the second 3-day food record will be obtained to evaluate changes in physical activity and food habits, respectively. The second mixed meal tolerance test will be performed following the same procedures as visit 2. Participants will be asked to return the empty bottles to quantify adherence to the intervention. In addition, adherence and symptoms formats will be collected.

Visit 4

Participants will be asked to assist one month after visit 3 to make a final evaluation of fasting glucose, insulin, and lipid profile concentrations. The physical activity questionnaire will be applied again, and a third 3-day food record will be collected to evaluate changes in physical activity and food habits, respectively.

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Mexico
      • Mexico City, Mexico, 14080
        • Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
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
Cornstarch without significant physiological effects
Experimental: Sucralose
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
Food additive used to replace sugar providing a sweet taste without calories.
Other Names:
  • non-nutritive sweetener

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
GLP-1
Time Frame: baseline and 30 days after the intervention
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
Time Frame: baseline and 30 days after the intervention
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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
C-peptide
Time Frame: baseline and 30 days after the intervention
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
C-reactive protein
Time Frame: baseline and 30 days after the intervention
To determine the effects of sucralose consumption in C-reactive protein concentrations in comparison to placebo
baseline and 30 days after the intervention
IL-6
Time Frame: baseline and 30 days after the intervention
To determine the effects of sucralose consumption in IL-6 concentrations in comparison to placebo
baseline and 30 days after the intervention
Tumor necrosis factor-alpha
Time Frame: baseline and 30 days after the intervention
To determine the effects of sucralose consumption in tumor necrosis factor-alpha concentrations in comparison to placebo
baseline and 30 days after the intervention
glucose
Time Frame: baseline and 30 days after the intervention
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
Time Frame: baseline and 30 days after the intervention
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
lipopolysaccharide
Time Frame: baseline and 30 days after the intervention
To determine the effects of sucralose consumption in lipopolysaccharide concentrations in comparison to placebo
baseline and 30 days after the intervention

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2023

Primary Completion (Actual)

February 29, 2024

Study Completion (Actual)

March 1, 2024

Study Registration Dates

First Submitted

October 17, 2023

First Submitted That Met QC Criteria

October 17, 2023

First Posted (Actual)

October 23, 2023

Study Record Updates

Last Update Posted (Actual)

March 12, 2024

Last Update Submitted That Met QC Criteria

March 8, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • 2635.2

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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