Sucralose and Glucose Metabolism in Young Healthy Adults

NCT07194772 | Completed

• 2 other identifiers: H-04-20-5636GR005077
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

This study aimed to investigate the effects of a three-week consumption of sucralose-sweetened beverages (low-calorie sweetener) on postprandial glycemic responses in healthy adults, compared with sugar-sweetened beverages under real-world conditions. In brief, postprandial glycemic responses are used as an indicator of how your body manages blood sugar levels after consuming glucose. To explore potential mechanisms underlying any observed changes in postprandial glycemic responses, we further investigated potential alterations in gut microbiota composition and functionality, as well as plasmatic biomarkers of intestinal permeability and systemic low-grade inflammation. Finally, this project explored whether free sugars derived from a natural source (100% natural fruit juice) elicit metabolic responses that differ from those of refined sugars. Participants visited the laboratory for a preliminary screening session to assess eligibility prior to being randomly assigned to one of the three experimental groups consuming either sucralose-sweetened beverages (LCS), sucrose-sweetened beverages (SSB), or 100% natural fruit juice (FJ) at dosage approximating real-world consumption over three weeks. Participants underwent two experimental sessions (duration of 3 hours each) at the beginning and completion of the study as outlined below.

Conditions

Gut Microbiota Dysbiosis and Nutrition; Glucose Intolerance; Glucose and Insulin Response; Glucose Homeostasis; Low-grade Inflammation; Intestinal Permeability; Gut Microbiota Diversity and Composition; Gut Microbiota Modulation; Gut Microbiota Dysbiosis; Gut Microbiota; Insulin Resistance; Insulin Sensitivity/Resistance; Insulin Sensitivity

Keywords

low-calorie sweeteners; sucralose; natural sugars; fruit juice; refined sugars; sugar-sweetened beverages; LCS; SSB; non-nutritive sweeteners; sugar substitutes; gut microbiota; low-calorie sweeteners and gut microbiota; low-calorie sweeteners and glycemic responses; sucralose and gut microbiota; sucralose and glycemic responses

Outcome Measures

Primary Outcomes (1)

• Change from Baseline in Postprandial Glycemic Responses

  Postprandial Glycemic Responses (plasma glucose concentrations) were assessed using a 2-hour 75g Oral Glucose Tolerance Test (OGTT) at baseline (day 0) and post-intervention (day 22)

  3 weeks

Secondary Outcomes (5)

• Change from Baseline in Postprandial Insulinemic Responses

  3 weeks

• Change from Baseline in Plasmatic Biomarkers of Intestinal Permeability

  3 weeks

• Change from Baseline in Plasmatic Biomarkers of Systemic Low-grade Inflammation

  3 weeks

• Change from Baseline in Fecal Concentrations of Short-Chain Fatty Acids and Branched-Chain Fatty Acids

  3 weeks

• Change from Baseline in Alpha-diversity and Beta-diversity of the Fecal Microbiota

  3 weeks

Study Arms (3)

Sucralose-sweetened beverages (low-calorie sweetener)

EXPERIMENTAL

Other: Low-calorie sweeteners (LCS)

Sugar-sweetened beverages (refined sugars)

EXPERIMENTAL

Other: Refined sugars (SSB)

Natural fruit juice (natural sugars)

EXPERIMENTAL

100% natural orange juice

Other: Natural sugars (FJ)

Interventions

Low-calorie sweeteners (LCS) OTHER

Consumption of sucralose-sweetened beverages (LCS) using doses and formulations reflecting real-world conditions. Individualized dose equivalent volume (mL) to SSB group. Average dose received of 150 mg (±30 mg) of pure sucralose per day (2.00 ± 0.23 mg/Kg BW) among participants, which is below Acceptable Daily Intake for sucralose (5 mg/Kg BW/day). LCS matched for sweetness to SSB based on the manufacturer's information.

Sucralose-sweetened beverages (low-calorie sweetener)

Refined sugars (SSB) OTHER

Consumption of sugar-sweetened beverages (SSB) using doses and formulations reflecting real-world conditions. Individualized dose of 15% Ereq representing estimated free sugars consumption in Canada. SSB matched total free sugar concentration of 100% natural orange juice (FJ).

Sugar-sweetened beverages (refined sugars)

Natural sugars (FJ) OTHER

Consumption of natural fruit juice (100% natural orange juice) using doses and formulations reflecting real-world conditions. Individualized dose of 15% Ereq representing estimated free sugars consumption in Canada.

Natural fruit juice (natural sugars)

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Ages 18-35 y
• Body mass index (BMI) between 18.0 and 34.9 kg/m2
• Waist circumference \< 102cm (men) and \< 88cm (women)
• Self-reported stable weight during the prior 6 months (+ or - 2kg) of beginning the study.
• Women using no form of hormonal contraception or using copper intrauterine device (IUD) required to report having a regular menstrual cycle to be included
• Women using anovulants (birth control pills) were advised to take their daily anovulant continuously for a period of 28 days to ensure stable hormone levels throughout the study (informed consent was obtained). Oral contraceptives release a low and stable daily amount of progestins, which were reported to have minor or no effects on glycemic responses of pre-menopausal women in a recent meta-analysis (Silva-Bermudez 2020).
• Women using hormonal contraception such as hormonal IUD and subdermal contraceptive implant were included regardless of their menstrual cycle. Like anovulants, hormonal IUD release a low and stable amount of a progestin (levonorgestrel) into the uterus, therefore preventing periodic fluctuations in hormonal levels during the menstrual cycle. Since Levonorgestrel was included as one of the progestins in the aforementioned meta-analysis, it was therefore assumed that HIUD would also not have a significant impact on glycemic responses, especially as its effect is local rather than systemic; Women using medroxyprogesterone acetate injections (Depo-Provera shot) were excluded given the pro-inflammatory effects associated with high doses of progestin
• Women experiencing pregnancy or lactation were excluded.

You may not qualify if:

• Prediabetes (fasting glucose ≥ 6.1 mmol/L)
• diabetes (fasting glucose ≥ 7.0 mmol/L)
• hypertension (\> 140/90 mmHg)
• Reported medical history for dyslipidemias (including hypercholesterolemia and hypertriglyceridemia)
• Surgery for weight loss
• Individuals who smoke tobacco (including vaping), habitually ingest \>2 alcoholic beverages/day and/or use cannabis or cannabis-derived products \>1 time/month
• Individuals who exercise \>3.5 h/week at a level more vigorous than walking
• Individuals who use thyroid, lipid-lowering, glucose-lowering, antihypertensive, antidepressant/antianxiety, antibiotics in the prior 3 months or weight-loss medications
• Individuals susceptible to exhibit clinically relevant levels of food cravings as indicated by a score \> 50 on the Food Cravings Questionnaire - Trait reduced (FCQ-T-r)36. FCQ-T-r (15 items) is a validated questionnaire37 that assesses four factors: (1) preoccupation with food (i.e., obsessive thought about food and eating), (2) loss of control (i.e., difficulty regulating eating behavior when exposed to food cues), (3) positive outcome expectancy (i.e., believing eating to be positively reinforcing), and (4) emotional craving (i.e., tending to crave food when experiencing negative emotion).

Sponsors & Collaborators

• University of Ottawa: lead

Study Sites (1)

Behavioural and Metabolic Research Unit, School of Human Kinetics, Faculty of Health Sciences, University of Ottawa

Ottawa, Ontario, K1S 5S9, Canada

Location

MeSH Terms

Conditions

Glucose Intolerance; Insulin Resistance

Interventions

SSB protein, human

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: randomized parallel-group design stratified by sex

Study Record Dates

• First Submitted: September 18, 2025
• First Posted: September 26, 2025
• Study Start: March 16, 2022
• Primary Completion: June 12, 2024
• Study Completion: June 12, 2024
• Last Updated: May 12, 2026

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 1 year after publication and available for 2 years.
• Access Criteria: Available to qualified researchers upon request (via institutional repository or upon request to the PI) and approval of a research proposal and data sharing agreement.

Locations

CA (1)