Effects of Low/No Calorie Sweeteners on Glucose Tolerance
Condition: Healthy Population; Glucose Tolerance
Study type: Interventional

Summary: 
      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: 
      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.
    

Intervention name(s): Low/No Calorie Sweeteners; Placebo Group
Intervention type(s): Other; Other
Intervention description(s): LNCS powdered and then dissolved in water.; Water
Other intervention name(s): Control
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention 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 (Participant, Investigator)
Primary purpose: Screening
Keywords: artificial sweeteners; non-nutritive sweeteners; oral glucose tolerance; glucagon-like peptide-1; insulin secretion; satiety peptides