SweetSpot - The Effect of Non-nutritive Sweeteners on Glucose Regulation, Gut Microbiome, and Gut Hormone Secretion in Healthy Adults: a Fully Controlled Cross-over Intervention Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Difference in change in 2h iAUC glucose after 6 weeks between the intervention and the control.
研究概览
简要总结
The aim of the study is to investigate the effect of non-nutritive sweeteners on glucose regulation. Secondary objectives are to investigate the effect of NNS on gut microbiome, gut hormone secretion, sweet taste sensitivity and preference, and the excretion of NNS in urine.
详细描述
Sugar intake has increased over the years, simultaneously with the prevalence of overweight and obesity. To decrease sugar intake, consumption of non-nutritive sweeteners (NNS) has increased and opinions on its use remain divided. A fully controlled dietary intervention using a NNS mixture and dose that is similar to real-life intake, is therefore necessary to advance our understanding of the potential effects of NNS on glucose regulation, gut microbiome, and gut hormone secretion under real-life conditions.
The aim of this study is to investigate the effect of non-nutritive sweeteners on glucose regulation. Secondary objectives are to investigate the effect of NNS on gut microbiome, gut hormone secretion, sweet taste sensitivity and preference, and the excretion of NNS in urine.
To do this, a single blind, fully controlled dietary intervention with a cross-over design will be performed. The study will consist of 2x8 weeks of intervention, with a washout of > 6 weeks in between. The study population will be 60 healthy adults aged 45-79, with a BMI between 20-35 kg/m2.
The study will consist of a fully controlled diet of two 8-week intervention periods (2 weeks run-in + 6 weeks intervention). The diets differ in the presence of non-nutritive sweeteners (NNS): NNS-diet versus non-NNS diet, where additional NNS are added to the NNS-diet.
The primary outcome measure will be the within person difference in blood glucose incremental area under the curve following a 75 g glucose tolerance test between the NNS diet and the non-NNS diet. Secondary outcome measures are the effect of NNS on Matsuda index, insulin response, blood lipid profile, and gut hormone secretion will be determined. The effect of NNS on small- and large intestinal microbiome will be investigated by a change in composition, functionality, and short chain fatty acid content. The effect of NNS on sweet taste sensitivity, preference, and liking will be investigated, as well as the excretion of NNS in urine and saliva.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- Single (Investigator)
入排标准
- 年龄范围
- 45 Years 至 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age 45-79 years;
- •BMI of 20-35 kg/m2;
- •Having veins suitable for placement of a venflon catheter.
排除标准
- •Diseases or prior surgeries affecting the stomach, liver, kidneys or intestines (allowed i.e. appendectomy);
- •Cardiovascular diseases (e.g. heart failure) or cancer (e.g. non-invasive skin cancer allowed);
- •Diagnosed with type 1 or type 2 diabetes;
- •Drug treated thyroid diseases (well substituted hypothyroidism is allowed for inclusion);
- •HbA1c level >6.5% (>48 mmol/mol), as measured during the screening visit;
- •Anaemia defined as Hb concentrations <8.5 mmol/L for men and <7.5 mmol/L for women via finger prick;
- •Regular use of/receiving medication interfering with research outcomes (as judged by research physician), such as use of glucose lowering drugs, insulin, or use of medication that impacts the gastro-intestinal system;
- •Use of antibiotics over the last 3 months before study start;
- •Donated blood within 2 months prior to the screening;
- •Food allergies, intolerances (including lactose/gluten intolerance) for products used in the study design and/or dietary restrictions interfering with the study (including special diets and eating disorders);
- •Followed a diet that can interfere with the study outcomes within 1 month prior to the screening (e.g. ketogenic, sugar free, carbohydrate free);
- •Not willing to eat all products in the study diet, including eggs and dairy. Vegetarian is possible;
- •Not willing to consume non-nutritive sweeteners;
- •Not willing to quit the use of supplements that can interfere with the study outcomes (e.g. pre- or probiotics).
- •Intention to change the intensity of exercise during the study period or planning to join a intensive sport event (e.g. marathon or triathlon);
- •Intention to lose or gain weight;
- •Working night shifts regularly;
- •Smoking regularly
- •Use of soft and/or hard drugs (cannabis included);
- •Abuse of alcohol (defined as >14 glasses (women) or >21 glasses (men) of alcoholic beverages per week);
- •Being pregnant or lactating or planning to become pregnant;
- •Inability to understand study information and/or communicate with staff;
- •Participation in another study that involves an intervention within two months prior to the intervention;
- •Working or doing a thesis/internship at the division of Human Nutrition & Health, or the Food, Health & Consumer Research group of Wageningen Food & Biobased Research.
研究组 & 干预措施
NNS / no-NNS
In this arm, participants will first receive the NNS diet, and the no-NNS diet in the second study period.
干预措施: Diet without non-nutritive sweeteners (Other)
NNS / no-NNS
In this arm, participants will first receive the NNS diet, and the no-NNS diet in the second study period.
干预措施: Diet with non-nutritive sweeteners (Other)
No-NNS / NNS
In this arm, participants will first receive the no-NNS diet, and the NNS diet in the second study period.
干预措施: Diet with non-nutritive sweeteners (Other)
No-NNS / NNS
In this arm, participants will first receive the no-NNS diet, and the NNS diet in the second study period.
干预措施: Diet without non-nutritive sweeteners (Other)
结局指标
主要结局
Difference in change in 2h iAUC glucose after 6 weeks between the intervention and the control.
时间窗: Week 2 and week 8 in both intervention periods (4 times in total)
The primary outcome measure is the difference in change in iAUC of blood glucose levels following a 2-hour oral glucose tolerance test (OGTT) after six weeks between the intervention period and the control period.
次要结局
- Fasting blood glucose(Baseline & 2 times per intervention period (week 2 and week 8). 5 times in total.)
- Matsuda index(Week 2 and week 8 in both intervention periods (4 times in total))
- Fasting blood insulin(Baseline & 2 times per intervention period (week 2 and week 8). 5 times in total.)
- Postprandial insulin response(Week 2 and 8 in both intervention periods (4 times in total).)
- Postprandial glucose response after a breakfast(Week 7 in both study periods (2 times in total))
- Blood lipid profile(Baseline & 2 times per intervention period (week 2 and week 8). 5 times in total.)
- Gut microbiota composition(Average of three samples per timepoint. Measured at baseline & 2 times per intervention period (week 2 and week 8). 15 samples over 5 timepoints in total.)
- Gut microbiota function(Average of three samples per timepoint. Measured at baseline & 2 times per intervention period (week 2 and week 8). 15 samples over 5 timepoints in total.)
- Microbial metabolites(Average of three samples per timepoint. Measured at baseline & 2 times per intervention period (week 2 and week 8). 15 samples over 5 timepoints in total.)
- Small intestinal microbiota composition(Week 7 of both intervention periods (2 times in total).)
- Gastro-intestinal transit time(Baseline & week 7 of both intervention periods (3 times in total).)
- Oral microbiome composition & function(Baseline & 2 times per intervention period (week 2 and week 8). 5 times in total.)
- Postprandial GLP-1 secretion(Week 2 and 8 of both intervention periods (4 times in total).)
- Postprandial GIP secretion(Week 2 and 8 of both intervention periods (4 times in total).)
- Sweetness-liker phenotype(Baseline & 2 times per intervention period (week 2 and week 8). 5 times in total.)
- Sweetness preference & liking(Baseline & 2 times per intervention period (week 2 and week 8). 5 times in total.)
- Sweet taste sensitivity(Baseline & 2 times per intervention period (week 2 and week 8). 5 times in total.)
- Excretion of NNS in urine(Baseline, week 2 and week 8 in intervention period 1, and every two weeks in intervention period 2 (7 times in total).)
- Excretion of NNS in saliva(Baseline & 2 times per intervention period (week 2 and week 8). 5 times in total.)
研究者
Monica Mars
Principal Investigator
Wageningen University