Effects of Low/No Calorie Sweeteners on Glucose Tolerance

Acibadem University

Status: Completed

Conditions: Healthy Population; Glucose Tolerance

Treatments: Other: Low/No Calorie Sweeteners; Other: Placebo Group

Study type: Interventional

Funder types: Other

Identifiers

NCT04904133

218S378 (Other Grant/Funding Number)

28850

Details and patient eligibility

About

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).

Full 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.

Enrollment: 42 patients

Sex: Female

Ages: 19 to 45 years old

Volunteers: Accepts Healthy Volunteers

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)

Trial design

Primary purpose: Screening

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

42 participants in 4 patient groups, including a placebo group

Saccharine Group

Active Comparator group

Description:

140 mg saccharin (Hermesetas) dissolved in 330 mL water for 4 weeks.

Treatment:

Other: Low/No Calorie Sweeteners

Sucralose Group

Active Comparator group

Description:

66 mg sucralose (Splenda) dissolved in 330 mL water for 4 weeks.

Treatment:

Other: Low/No Calorie Sweeteners

Aspartame+Acesulfame-K Group

Active Comparator group

Description:

88 mg aspartame+88 mg acesulfame-K (Takita) dissolved in 330 mL water for 4 weeks.

Treatment:

Other: Low/No Calorie Sweeteners

Control Group

Placebo Comparator group

Description:

330 mL water for 4 weeks.

Treatment:

Other: Placebo Group