Changes in Gut Microbiota and Postprandial GLP-1 Concentration Due to Sucralose Consumption
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- glucose
研究概览
简要总结
Recently, it has been proposed that the consumption of non-nutritive sweeteners, including sucralose, it's not harmless and is related with metabolic effects. Some studies have reported that sucralose produces alterations in glucose homeostasis. In vitro studies indicate that sucralose can interact with sweet taste receptors (T1R2 and T1R3) in the intestine, thus increasing the expression of glucose transporters including the sodium-glucose cotransporter type 1 (SGLT1) and the glucose transporter 2 (GLUT2), increasing glucose absorption. This interaction with intestinal sweet taste receptors also generates an increase in the secretion of the incretins glucagon-like peptide type 1 (GLP-1) and the glucose-dependent insulinotropic polypeptide (GIP), which might enhance the postprandial insulin release. However, these results are preliminary and it's desirable to confirm if sucralose consumption is associated with glucose metabolism modifications using an appropriate methodological design and with gold standard methods. The aim of this triple-blind, placebo-controlled, parallel, randomized clinical trial is to confirm the changes in insulin sensitivity associated with sucralose consumption in humans, to identify whether these changes are in the liver or skeletal muscle and to investigate the pathophysiological mechanisms generating these changes. Specifically, we will investigate if sucralose generates a dysbiosis in the gut microbiota that could be related to insulin resistance by increasing concentrations of lipopolysaccharide, a toxin found in Gram-negative bacteria that triggers a low-grade inflammation known as metabolic endotoxemia. In addition, the changes in postprandial concentrations of GLP-1, glucose, insulin, and C-peptide due to the combination of sucralose with a mixed meal will be investigated. The results of this study will determine if sucralose consumption, frequently used as a non-nutritive sweetener, is associated to significant changes in glucose homeostasis in humans.
详细描述
Study design:
This is a triple-blind, parallel, placebo-controlled, randomized clinical trial.
Sample size:
The sample size was calculated to observe a difference of 20% in the Matsuda index between groups.
The calculation was done considering a probability of type I error (α) of 5%, with a power of 80% and adding an extra-20% for potential losses at follow-up.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The use of identical capsules will allow the blinding, the capsules will be deposited in bottles numbered sequentially according to the enrollment process and neither the participants nor the researchers will know the content of the capsules, or the group assigned.
入排标准
- 年龄范围
- 20 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Normal BMI (18.5-24.9 kg/m2)
- •Low habitual consumption of non-nutritive sweeteners (NNS
- •Fasting plasma insulin concentration of <12 mU/L
排除标准
- •Diabetes or altered glucose metabolism (abnormal fasting glucose, glucose intolerance or elevated glycated hemoglobin)
- •Use of antibiotics in the last 3 months
- •Use of probiotics through pharmaceutical products
- •Liver or kidney disease
- •Use of medications that could interfere with insulin sensitivity
- •Severe intestinal diseases
- •History of bariatric surgery
- •Pregnancy or lactation
研究组 & 干预措施
Sucralose
The intervention will consist of capsules filled with pure sucralose. Each capsule will contain 90 mg of sucralose. Participants will be asked to consume one capsule in each meal (three per day) to achieve an ingestion of 270 mg of sucralose, this quantity corresponds approximately to the 30% of the acceptable daily intake (ADI) of sucralose for a lean person. This was calculated based on the ADI established by the joint FAO/WHO expert committee on food additives (JECFA) of 15 mg per kg of body weight per day of sucralose.
干预措施: sucralose (Other)
Placebo
The intervention will consist of capsules filled with placebo (cornstarch). Each capsule will contain 90 mg of cornstarch. Participants will be asked to consume one capsule in each meal (three per day) in order to achieve an ingestion of 270 mg of placebo, this quantity is in order to match the sucralose consumed in the intervention group.
干预措施: placebo (Other)
结局指标
主要结局
glucose
时间窗: baseline and 30 days after the intervention
To evaluate the changes in postprandial glucose concentrations during a mixed meal after sucralose consumption in comparison to placebo
insulin
时间窗: baseline and 30 days after the intervention
To evaluate the changes in postprandial insulin concentrations during a mixed meal after sucralose consumption in comparison to placebo
C-peptide
时间窗: baseline and 30 days after the intervention
To evaluate the changes in postprandial C-peptide concentrations during a mixed meal after sucralose consumption in comparison to placebo
GLP-1
时间窗: baseline and 30 days after the intervention
To evaluate the changes in postprandial GLP-1 area under the curve during a mixed meal after sucralose consumption in comparison to placebo
gut microbiota
时间窗: baseline and 30 days after the intervention
To compare the change in the relative abundance of colony forming units of bacterial genus and species after sucralose consumption in comparison to placebo through messenger RNA sequencing
PYY
时间窗: baseline and 30 days after the intervention
To evaluate the changes in postprandial PYY area under the curve during a mixed meal after sucralose consumption in comparison to placebo
ghrelin
时间窗: baseline and 30 days after the intervention
To evaluate the changes in postprandial ghrelin area under the curve during a mixed meal after sucralose consumption in comparison to placebo
次要结局
- lipopolysaccharide(baseline and 30 days after the intervention)
- C-reactive protein(baseline and 30 days after the intervention)
- IL-6(baseline and 30 days after the intervention)
- tumor necrosis factor-alpha(baseline and 30 days after the intervention)
研究者
Paloma Almeda-Valdés
MD, PhD
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran