Effects of Sweetener Consumption on Risk Factors for Heart Disease in Prediabetic Subjects (Sweetheart)

January 22, 2026 updated by: Marco Witkowski, Charite University, Berlin, Germany

Effects of Sweetener Consumption on Risk Factors for Heart Disease

The aim of this prospective interventional study is to investigate the metabolic effects of consuming artificial and natural sweeteners in persons with prediabetes. Prediabetes is a condition characterized by blood sugar levels that are elevated above normal but not yet meeting the criteria for type 2 diabetes. This condition markedly increases the risk of progressing to type 2 diabetes, which in turn can lead to complications including cardiovascular diseases.

Artificial sweeteners such as saccharin and sucralose, as well as natural sugar substitutes like erythritol, are increasingly used as alternatives to sugar and are recommended for individuals at cardiometabolic risk - including overweight individuals, patients with prediabetes, or diabetics - to help reduce caloric intake. Recent literature has reported possible negative associations between artificial sweeteners and blood sugar regulation in healthy subjects (1). Additionally, effects on various blood cells have been observed. For example, erythritol has been shown to alter platelet function leading to increased reactivity in healthy study participants following consumption (2).

However, the impact of alternative sweeteners on metabolic processes and their effects on blood coagulation in patients with prediabetes-a population at increased risk-has not been systematically studied. In this planned interventional study, 80 patients meeting laboratory criteria for prediabetes will be randomly assigned to one of four groups, each receiving a different intervention for two weeks: saccharin, sucralose, erythritol, or a control group receiving water. The doses reflect the acceptable daily intake or known doses that are considered safe.

After enrollment, participants will visit the study center 2 times: before starting the intervention and after completing the intervention. During these visits, biological samples such as blood, urine, and stool will be collected to study metabolism, gut bacteria, immune and blood cell function. Tests will include an oral glucose tolerance test, coagulation tests, and additional blood analyses. Additionally, participants will wear a glucose monitor to track blood sugar fluctuations during the intervention.

The investigators hypothesize that consumption of alternative sweeteners negatively affects blood sugar regulation and insulin sensitivity in patients with prediabetes. Furthermore, this study will explore how the candidate sweeteners influence the gut microbiome, blood cells and other metabolic factors in this population.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

80

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Marco Witkowski, MD, PhD
  • Phone Number: +49 (0)30 450543775
  • Email: fs-cpc@charite.de

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Presence of prediabetes (HbA1c 5.7-6.4% or glucose after oral glucose tolerance test 140 to 199 mg/dL)
  • Written informed consent available

Exclusion Criteria:

  • Inability to communicate sufficiently in the required language
  • Dementia or other significantly cognitively impairing condition
  • Current pregnancy or breastfeeding
  • Other severe internal, neurological, or psychiatric condition
  • History of gout
  • History of gallstones / diagnosis of cholelithiasis

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Saccharin Group
Intervention: Saccharin
Dietary supplement: Saccharin
Participants in the saccharin group will consume 5 mg/kg body weight of saccharin daily, dissolved in 500 mL of water. This corresponds to the maximum recommended daily intake as determined by EFSA and JECFA (the joint FAO/WHO Expert Committee on Food Additives).
Active Comparator: Sucralose Group
Intervention: Sucralose
Dietary supplement: Sucralose
Participants in the sucralose group will consume 15 mg/kg body weight of sucralose daily in 500 mL of water, representing the maximum recommended daily intake.
Active Comparator: Erythritol Group
Intervention: Erythritol
Dietary supplement: Erythritol
Those in the erythritol group will consume 0.5 g/kg body weight of erythritol daily in 500 mL of water, a dose considered safe and below levels that cause digestive discomfort (European Food Safety Authority [EFSA], 2023).
Placebo Comparator: Control Group
Intervention: Vehicle
Dietary supplement: Vehicle
Participants in the control group (vehicle) will receive a vehicle consisting of 500 mL unsweetened lemon soda

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change of glucose tolerance
Time Frame: Baseline vs. within 1 week after intervention
Measured by AUC of oral glucose tolerance test
Baseline vs. within 1 week after intervention

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change of microbiome
Time Frame: Baseline vs. within 1 week after intervention
RNA-Sequencing of stool samples
Baseline vs. within 1 week after intervention
Flow cytometry analysis of changes in frequency of circulating monocyte subsets (%)
Time Frame: Baseline vs. within 1 week after intervention
Measured by flow cytometry in isolated PBMCs (Peripheral Blood Mononuclear Cells) using specific antibodies with binding to CD45, CD14, CD15 and CD16 to define monocyte subsets. Values will be reported as percent of CD45+ leukocytes
Baseline vs. within 1 week after intervention
Flow cytometry analysis of changes in platelet activation marker expression (% positive platelets)
Time Frame: Baseline vs. within 1 week after intervention
Whole blood samples will be analyzed using flow cytometry. Platelets will be detected based on size and using well-established surface markers (CD41). Activation markers will be assessed (CD62P and PAC1) and reported as percent of positive cells.
Baseline vs. within 1 week after intervention
Flow cytometry analysis of changes in platelet activation marker expression (MFI)
Time Frame: Baseline vs. within 1 week after intervention
Whole blood samples will be analyzed using flow cytometry. Platelets will be detected based on size and using well-established surface markers (CD41). Activation markers will be assessed (CD62P and PAC1) and reported as mean fluorescence intensity.
Baseline vs. within 1 week after intervention
Changes in lipid profile
Time Frame: Baseline vs. within 1 week after intervention
Serum analysis of Total cholesterol, HDL and LDL cholesterol, triglycerides
Baseline vs. within 1 week after intervention
Changes in blood metabolite profiles by liquid chromatography / mass spectrometry
Time Frame: Baseline vs. within 1 week after intervention
Untargeted metabolomics analysis of plasma samples using liquid chromatography-mass spectrometry (LC/MS). Data will be reported as relative ion intensity changes from baseline (log2 fold change, mean ± SD) for significantly altered features.
Baseline vs. within 1 week after intervention
Changes in body mass index (BMI)
Time Frame: Baseline vs. within 1 week after intervention
To observe changes in anthropometric measures. Measurement of height in meters and weight in kilograms to calculate body mass index (BMI = weight/height^2) in kg/m^2
Baseline vs. within 1 week after intervention
Changes in waist to hip ratio (WHR)
Time Frame: Baseline vs. within 1 week after intervention
To observe changes in anthropometric measures. Measurement of waist circumference and hip circumference to calculate waist-to-hip-ratio WHR (waist circumference divided by hip circumference).
Baseline vs. within 1 week after intervention
Changes in body fat percentage
Time Frame: Baseline vs. within 1 week after intervention
Measured by Bioelectrical Impedance Analysis (BIA)
Baseline vs. within 1 week after intervention

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Charite University, Berlin, Germany

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

January 5, 2026

Primary Completion (Estimated)

November 1, 2026

Study Completion (Estimated)

November 1, 2026

Study Registration Dates

First Submitted

December 11, 2025

First Submitted That Met QC Criteria

January 22, 2026

First Posted (Actual)

January 29, 2026

Study Record Updates

Last Update Posted (Actual)

January 29, 2026

Last Update Submitted That Met QC Criteria

January 22, 2026

Last Verified

December 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Sweetheart-Study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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