Effects of Low/No Calorie Sweeteners on Glucose Tolerance

NCT ID: NCT04904133

Last Updated: 2021-05-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

42 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-04-02

Study Completion Date

2019-07-02

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.

Conditions

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Healthy Population Glucose Tolerance

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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
Primary Study Purpose

SCREENING

Blinding Strategy

DOUBLE

Participants Investigators
Participants were not informed about the study group and also which sweetener they consumed.

Study Groups

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Saccharine Group

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

Group Type ACTIVE_COMPARATOR

Low/No Calorie Sweeteners

Intervention Type OTHER

LNCS powdered and then dissolved in water.

Sucralose Group

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

Group Type ACTIVE_COMPARATOR

Low/No Calorie Sweeteners

Intervention Type OTHER

LNCS powdered and then dissolved in water.

Aspartame+Acesulfame-K Group

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

Group Type ACTIVE_COMPARATOR

Low/No Calorie Sweeteners

Intervention Type OTHER

LNCS powdered and then dissolved in water.

Control Group

330 mL water for 4 weeks.

Group Type PLACEBO_COMPARATOR

Placebo Group

Intervention Type OTHER

Water

Interventions

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Low/No Calorie Sweeteners

LNCS powdered and then dissolved in water.

Intervention Type OTHER

Placebo Group

Water

Intervention Type OTHER

Other Intervention Names

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Control

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)
Minimum Eligible Age

19 Years

Maximum Eligible Age

45 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Acibadem University

OTHER

Sponsor Role lead

Responsible Party

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Şaziye Ecem Örkü

Ph.D, Department of Nutrition and Dietetics, Acıbadem University

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Saziye E Orku, Dr.

Role: PRINCIPAL_INVESTIGATOR

Acibadem University

Locations

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Acıbadem Dr. Şinasi Can (Kadıköy) Hospital

Istanbul, Anadolu, Turkey (Türkiye)

Site Status

Countries

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Turkey (Türkiye)

References

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Suez J, Korem T, Zeevi D, Zilberman-Schapira G, Thaiss CA, Maza O, Israeli D, Zmora N, Gilad S, Weinberger A, Kuperman Y, Harmelin A, Kolodkin-Gal I, Shapiro H, Halpern Z, Segal E, Elinav E. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature. 2014 Oct 9;514(7521):181-6. doi: 10.1038/nature13793. Epub 2014 Sep 17.

Reference Type BACKGROUND
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Reference Type BACKGROUND
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Jang HJ, Kokrashvili Z, Theodorakis MJ, Carlson OD, Kim BJ, Zhou J, Kim HH, Xu X, Chan SL, Juhaszova M, Bernier M, Mosinger B, Margolskee RF, Egan JM. Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1. Proc Natl Acad Sci U S A. 2007 Sep 18;104(38):15069-74. doi: 10.1073/pnas.0706890104. Epub 2007 Aug 27.

Reference Type BACKGROUND
PMID: 17724330 (View on PubMed)

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PMID: 22679063 (View on PubMed)

Nakagawa Y, Nagasawa M, Yamada S, Hara A, Mogami H, Nikolaev VO, Lohse MJ, Shigemura N, Ninomiya Y, Kojima I. Sweet taste receptor expressed in pancreatic beta-cells activates the calcium and cyclic AMP signaling systems and stimulates insulin secretion. PLoS One. 2009;4(4):e5106. doi: 10.1371/journal.pone.0005106. Epub 2009 Apr 8.

Reference Type BACKGROUND
PMID: 19352508 (View on PubMed)

Fujita Y, Wideman RD, Speck M, Asadi A, King DS, Webber TD, Haneda M, Kieffer TJ. Incretin release from gut is acutely enhanced by sugar but not by sweeteners in vivo. Am J Physiol Endocrinol Metab. 2009 Mar;296(3):E473-9. doi: 10.1152/ajpendo.90636.2008. Epub 2008 Dec 23.

Reference Type BACKGROUND
PMID: 19106249 (View on PubMed)

Sylvetsky AC, Brown RJ, Blau JE, Walter M, Rother KI. Hormonal responses to non-nutritive sweeteners in water and diet soda. Nutr Metab (Lond). 2016 Oct 21;13:71. doi: 10.1186/s12986-016-0129-3. eCollection 2016.

Reference Type BACKGROUND
PMID: 27777606 (View on PubMed)

Ma J, Bellon M, Wishart JM, Young R, Blackshaw LA, Jones KL, Horowitz M, Rayner CK. Effect of the artificial sweetener, sucralose, on gastric emptying and incretin hormone release in healthy subjects. Am J Physiol Gastrointest Liver Physiol. 2009 Apr;296(4):G735-9. doi: 10.1152/ajpgi.90708.2008. Epub 2009 Feb 12.

Reference Type BACKGROUND
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Temizkan S, Deyneli O, Yasar M, Arpa M, Gunes M, Yazici D, Sirikci O, Haklar G, Imeryuz N, Yavuz DG. Sucralose enhances GLP-1 release and lowers blood glucose in the presence of carbohydrate in healthy subjects but not in patients with type 2 diabetes. Eur J Clin Nutr. 2015 Feb;69(2):162-6. doi: 10.1038/ejcn.2014.208. Epub 2014 Oct 1.

Reference Type BACKGROUND
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Orku SE, Suyen G, Bas M. The effect of regular consumption of four low- or no-calorie sweeteners on glycemic response in healthy women: A randomized controlled trial. Nutrition. 2023 Feb;106:111885. doi: 10.1016/j.nut.2022.111885. Epub 2022 Nov 1.

Reference Type DERIVED
PMID: 36470113 (View on PubMed)

Other Identifiers

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218S378

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

28850

Identifier Type: -

Identifier Source: org_study_id

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