Serum Insulin Response After Acute and Chronic Sucralose Ingestion in Healthy Volunteers With Variable Body Mass Index
Condition: Healthy
Study type: Interventional

Summary: 
      The consumption of non-caloric sweeteners has increased worldwide; Current publications
      suggest its consumption associates to insulin resistance.

      The present study aims to demonstrate whether acute or chronic sucralose exposure affects
      insulin or carbohydrate metabolism or alters systemic inflammatory markers and microbiota in
      young, healthy adults.

      In this prospective, randomized, double-blind, placebo-controlled clinical trial, three
      groups will be included with 30 healthy volunteers each. Group A will receive sucralose 48
      mg/ day, group B 96 mg/day and group C plain water as placebo. Subjects will be exposed to
      acute (one day) and chronic (seventy days) oral sucralose ingestion. After acute or chronic
      exposure, volunteers will undergo into an Oral Glucose Tolerance Test (OGTT), taking blood
      samples at -15, 0, 15, 30, 45, 60, 75, 90, 105, 120 and 180 minutes, respectively.

      Areas under the curve (AUC) for insulin and glucose, will be calculated from zero to one
      hundred and eighty minutes as described; for C peptide, glucagon, GIP (glucose-dependent
      insulinotropic polypeptide) and GLP-1 (glucagon-like peptide) measure points will be at 0, 30
      and 60 minutes only. Differences between one and seventy days AUC means will be compared
      between the three groups, adjusting for BMI. Besides, initial and final systemic inflammatory
      markers and inflammatory monocytes levels will be quantified and compare between acute and
      chronic exposure. Also, a comparison between the percentage of acute and chronic microbiome
      bacterial population in feces will be made.
    

Detailed description: 
      Introduction Overweight and obesity have increased along with the rate of other
      non-communicable diseases worldwide. At the same time, the consumption of non-caloric
      sweeteners (NCS) has risen considerably among the general population. Although international
      organizations such as Joint FAO/WHO Expert Committee on Food Additives (JECFA) has
      demonstrated NCS are safe; two recent publications suggested its consumption associates with
      insulin resistance.

      Although the authors attributed the metabolic effect to changes in the composition of
      intestinal microbiota as a consequence of NCS ingestion, these studies lacked a robust
      clinical methodology, as their design were not randomized, comparative studies and the effect
      of NCS on systemic inflammation biomarkers were neglected.

      Outcomes The present study aims to demonstrate whether acute or chronic sucralose exposure
      affects insulin or carbohydrate metabolism or alters systemic inflammatory markers and
      microbiota in young, healthy adults.

      Materials and methods It is a prospective, randomized, double-blind, placebo-controlled
      clinical trial, comparing three groups, with 30 healthy volunteers each, who will receive
      daily sucralose, for seventy days. After signing off informed consent, the first group will
      take 48 mg sucralose diluted in 60 mL of water; the second group will receive 96 mg / 60 ml a
      day, while the last group will receive 60 ml of plain water as placebo.

      Inclusion criteria will be either sex, age between 18 and 35 years, with a body mass index
      (BMI) between 18.5 and 39.0, disease free, with light or moderate physical activity before
      entering the study, with a HOMA ≤3.8, non-smokers, non-alcohol drinkers, agreeing not to
      consume neither industrial food nor beverages related to NCS during the study, having Mexican
      ancestry, living in the Mexico City metropolitan area and signing informed consent to
      participate in the study.

      Exclusion criteria Any acute disease by the time of recruitment, history of Type 1 or 2
      diabetes, thyroid disease, adrenal glands disease, insulinoma, malabsorption syndrome, short
      bowel, HIV, any cancer, liver disease, renal disease, inflammatory bowel disease, have
      prescribed corticosteroids in the previous three months before enrollment or undergone to
      bariatric surgery. Having a BMI <18.5 or >39.0, working night shifts, unable to remain at the
      clinic for at least 5 hours, not accepting to stop consuming industrialized food or beverages
      containing NCS, not accepting to stop alcohol or tobacco consumption during the study, not
      consenting to participate, women in childbearing potential without pregnancy control or women
      pregnant or breastfeeding by the time of enrollment.

      Each volunteer will be instructed to drink 60 mL of fluid containing either sucralose or
      water, every morning before meals for seventy days. Except on day one and day 70, when they
      will be requested to attend the clinic after fasting at least 8 hours. Two plastic containers
      to carry stool sample will be provided in advance to each participant and be requested to
      store a stool sample. At their arrival to the clinic the stool sample will be collected and
      labeled. Immediately after, they will be asked to drink the corresponding dose to day one or
      seventy in the presence of the investigators. Once the investigational material be drinking,
      an Oral Glucose Tolerance Test (OGTT), will be initiated, taking blood samples at

        -  15, 0, 15, 30, 45, 60, 75, 90, 105, 120 and 180 minutes, respectively. Analysis
           Demographics per group will be described initially. Following, areas under the curve
           (AUC) for insulin and glucose, will be calculated from zero to one hundred and eighty
           minutes, as the measure points described above; for C peptide, glucagon, GIP
           (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide) measure
           points will be at 0, 30 and 60 minutes only.

      Mean differences of AUCs between one and seventy days will be compared between the three
      groups, adjusting for BMI. Besides, initial and final systemic inflammatory markers and
      inflammatory monocytes levels will be quantified and compared between acute and chronic
      exposure. Additionally, a comparison of changes between the percentage of acute and chronic
      microbiome population in feces will be made.
    

Intervention name(s): sucralose 48 mg (splenda)/day for ten weeks
Intervention type(s): Dietary Supplement
Intervention description(s): volunteers will take sucralose or placebo daily for 70 days
Other intervention name(s): sucralose 96 mg (splenda)/day for ten weeks; placebo
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Double (Participant, Care Provider)
Primary purpose: Screening
Keywords: sucralose; insulin; AUC; young; inflammatory markers; intolerance