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

Официальное название

Effects of Sweetener Consumption on Risk Factors for Heart Disease

Обзор

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.

Вмешательства

• Пищевая добавка 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).
• Пищевая добавка 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.
• Пищевая добавка 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).
• Пищевая добавка Vehicle
  Participants in the control group (vehicle) will receive a vehicle consisting of 500 mL unsweetened lemon soda

Первичные конечные точки

• Change of glucose tolerance [Срок оценки: Baseline vs. within 1 week after intervention]

Вторичные конечные точки (9)

• Change of microbiome [Срок оценки: Baseline vs. within 1 week after intervention]
• Flow cytometry analysis of changes in frequency of circulating monocyte subsets (%) [Срок оценки: Baseline vs. within 1 week after intervention]
• Flow cytometry analysis of changes in platelet activation marker expression (% positive platelets) [Срок оценки: Baseline vs. within 1 week after intervention]
• Flow cytometry analysis of changes in platelet activation marker expression (MFI) [Срок оценки: Baseline vs. within 1 week after intervention]
• Changes in lipid profile [Срок оценки: Baseline vs. within 1 week after intervention]
• Changes in blood metabolite profiles by liquid chromatography / mass spectrometry [Срок оценки: Baseline vs. within 1 week after intervention]
• Changes in body mass index (BMI) [Срок оценки: Baseline vs. within 1 week after intervention]
• Changes in waist to hip ratio (WHR) [Срок оценки: Baseline vs. within 1 week after intervention]
• Changes in body fat percentage [Срок оценки: Baseline vs. within 1 week after intervention]

Критерии участия

Критерии включения

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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Фундаментальное исследование

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

• 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

Идентификаторы

NCT: NCT07377097 · Sweetheart-Study

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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