Effects of Low/No Calorie Sweeteners on Glucose Tolerance

Study Overview
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Brief Summary
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This study aims to determine the effects of chronic exposure to some low/no calorie sweeteners (LNCS) on glucose tolerance and glucagon like peptide 1 (GLP-1) release in healthy individuals. LNCS examined in this study are saccharin, sucralose and aspartame+acesulfame-K. The amounts of LNCS given to the participants are kept similar to daily life exposure; far less than the Acceptable Daily Intakes (ADIs) levels proposed by Food and Drug Administration (FDA) or European Food Safety Authority (EFSA).

Detailed Description
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Excessive sugar consumption has been related to chronic metabolic problems, including obesity, type 2 diabetes, neuroinflammatory diseases, etc. Therefore, it is recommended to decrease added sugar intake below 10% of total energy intake. Low/no calorie sweeteners (LNCS) may seem as a good alternative to added sugars because they provide sweetness without adding calories to the diet. Although they may reduce energy intake and prevent weight gain, studies investigating the short and long term effects of these sweeteners on metabolic profile are controversial. Therefore, there is a need for future studies to shed light on metabolic effects of these compounds in humans. Some observational and clinical studies show that they may cause insulin resistance and type 2 diabetes. There are possible mechanisms that may explain this relationship. One of these possible mechanisms is interaction with sweet taste receptors (STRs). It has been shown that STRs not only found in oral cavity but also in extra-oral tissues, such as gastrointestinal tract, pancreas, brain, etc. In vitro studies with sucralose, it has been shown that it may activate STRs in L-cells and stimulate GLP-1 release in a similar manner with glucose. However, these results were not confirmed in vivo. There are at least six different LNCS approved for human use worldwide. However, each of them have different biological fate in terms of absorption, metabolism and excretion characteristics in the body. Therefore, result of a study with one of LNCS cannot be extrapolated for all LNCS; each of them should be studied in well-designed studies. In this study it is hypothesized that LNCS may activate STRs in intestinal L-cells and alter release of GLP-1; as a result impair glucose tolerance. In acute human studies, these effects are tested and there are controversial results in regard to glucose tolerance or incretin release. However, individuals who want to consume fewer calories or to better control their blood glucose use LNCS in place of sugar for longer period of time. For this reason, we wanted to test the effects of regular use of LNCS on glucose tolerance and incretin release.

Official Title
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The Effect of Regular Consumption of Low/No Calorie Sweeteners on Glycemic Response and Glucagon Like Peptide-1 Secretion in Healthy Adults: A Randomized Controlled Trial

Conditions
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Healthy Population, Glucose Tolerance

Intervention / Treatment
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* Other: Low/No Calorie Sweeteners
* Other: Placebo Group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy, Normoglycemic, Female, 19-45 years old, Weight-stable past 3 months Exclusion Criteria: Insulin resistance, Type 2 diabetes mellitus, Presence of acute/chronic infection, Use of medication that may affect glucose metabolism (thiazide diuretics, glucocorticoids, estrogen or beta blockers) Chronic alcohol intake, Regular consumption of diet soda (more than one can of soda per week)

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Volunteers were randomly divided into 4 groups (saccharin, sucralose, aspartame+acesulfame-K [Asp+Ace-K], control) and asked to drink the LNCS sweetened water once a day for 4-wks. All study groups and concentration of LNCS they consumed written as follows; Saccharin group: 330 mL water + 140 mg saccharine Sucralose group: 330 mL water + 66 mg sucralose Asp+Ace-K group: 330 mL water + 88 mg aspartame and 88 mg acesulfame-K Control group IV: 330 mL water only
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Saccharine Group<br>140 mg saccharin (Hermesetas) dissolved in 330 mL water for 4 weeks. | Other: Low/No Calorie Sweeteners<br>* LNCS powdered and then dissolved in water.<br>|
| Active Comparator: Sucralose Group<br>66 mg sucralose (Splenda) dissolved in 330 mL water for 4 weeks. | Other: Low/No Calorie Sweeteners<br>* LNCS powdered and then dissolved in water.<br>|
| Active Comparator: Aspartame+Acesulfame-K Group<br>88 mg aspartame+88 mg acesulfame-K (Takita) dissolved in 330 mL water for 4 weeks. | Other: Low/No Calorie Sweeteners<br>* LNCS powdered and then dissolved in water.<br>|
| Placebo Comparator: Control Group<br>330 mL water for 4 weeks. | Other: Placebo Group<br>* Water<br>* Other names: Control;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3 Hours Plasma Glucose | Change from baseline plasma glucose levels at 4 weeks observed. Participants underwent a 3-h oral glucose tolerance test (3-h OGTT) by consuming a 250 mL 75 g glucose solution, and blood samples were collected at 60, 120, 180 min. | 3 hours | 
| 3 Hours Plasma Insulin | Change from baseline insulin levels at 4 weeks observed. Participants underwent a 3-h oral glucose tolerance test (3-h OGTT) by consuming a 250 mL 75 g glucose solution, and blood samples were collected at 60, 120, 180 min. | 3 hours | 
| Glucagon-like peptide-1 (GLP-1) release | Change from baseline fasting GLP-1 levels at 4 weeks observed. | Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body Weight | Change from baseline body weight at 4 weeks observed. Participants were weighed on a digital scale (Tanita MC 180) in fasted state. Weights were expressed in kilograms (kg). | Week 4 | 
| Fat Mass | Change from baseline fat mass (kg) at 4 weeks observed. Fat mass was determined by bioelectrical impedance analysis (BIA) method (Tanita MC180). | Week 4 | 
| Fat-Free Mass | Change from baseline fat-free mass (kg) at 4 weeks observed. Fat-free mass was determined by bioelectrical impedance analysis (BIA) method (Tanita MC180). | Week 4 | 
| Total Body Water | Change from baseline total body water (kg) at 4 weeks observed. Total body water was determined by bioelectrical impedance analysis (BIA) method (Tanita MC180). | Week 4 | 
| Body Mass Index (BMI) | Change from baseline BMI at 4 weeks observed. BMI was calculated as weight (in kilograms) divided by the square of height (in meters). | Week 4 | 
| Waist Circumference | Change from baseline waist circumference (in centimeters) at 4 weeks observed. | Week 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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artificial sweeteners, non-nutritive sweeteners, oral glucose tolerance, glucagon-like peptide-1, insulin secretion, satiety peptides