Effects of Sweetener Consumption on Risk Factors for Heart Disease in Prediabetic Subjects
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Saccharin, Sucralose, Erythritol, Vehicle.
- Who it may be relevant to
- Registry conditions: Prediabetic State, Metabolic Syndrome, Insulin Resistance, Thrombosis. Basic parameters: 18 years — 75 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Center list to be confirmed — check the primary protocol.
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
Effects of Sweetener Consumption on Risk Factors for Heart Disease
Overview
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.
Interventions
- 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). - 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. - 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). - Dietary supplement Vehicle
Participants in the control group (vehicle) will receive a vehicle consisting of 500 mL unsweetened lemon soda
Primary outcome measures
- Change of glucose tolerance [Time frame: Baseline vs. within 1 week after intervention]
Secondary outcome measures (9)
- Change of microbiome [Time frame: 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]
- Flow cytometry analysis of changes in platelet activation marker expression (% positive platelets) [Time frame: 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]
- Changes in lipid profile [Time frame: 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]
- Changes in body mass index (BMI) [Time frame: Baseline vs. within 1 week after intervention]
- Changes in waist to hip ratio (WHR) [Time frame: Baseline vs. within 1 week after intervention]
- Changes in body fat percentage [Time frame: Baseline vs. within 1 week after intervention]
Eligibility criteria
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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Single blind
- Primary purpose
- Basic science
Study locations
Center list to be confirmed — check the primary protocol.
Publications
- Witkowski M, Wilcox J, Province V, Wang Z, Nemet I, Tang WHW, Hazen SL. Ingestion of the Non-Nutritive Sweetener Erythritol, but Not Glucose, Enhances Platelet Reactivity and Thrombosis Potential in Healthy Volunteers-Brief Report. Arterioscler Thromb Vasc Biol. 2024 Sep;44(9):2136-2141. doi: 10.1161/ATVBAHA.124.321019. Epub 2024 Aug 8. PMID 39114916
- Suez J, Cohen Y, Valdes-Mas R, Mor U, Dori-Bachash M, Federici S, Zmora N, Leshem A, Heinemann M, Linevsky R, Zur M, Ben-Zeev Brik R, Bukimer A, Eliyahu-Miller S, Metz A, Fischbein R, Sharov O, Malitsky S, Itkin M, Stettner N, Harmelin A, Shapiro H, Stein-Thoeringer CK, Segal E, Elinav E. Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance. Cell. 2022 Sep PMID 35987213
Identifiers
NCT: NCT07377097 · Sweetheart-Study