An interventional study of Diet with non-nutritive sweeteners and Diet without non-nutritive sweeteners in Healthy Adult, sponsored by Wageningen University. Recruiting at 1 site in Netherlands. Open to participants aged 45 Years to 79 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-07-14.
Sponsored by Wageningen University · Not applicable, Interventional, and Other
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.
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.
The total time invested by participants is around 85 hours. Participants are restricted for 16 weeks in their eating habits, since they follow a fully controlled diet prepared by the research facility. Participants will visit the research facility in total 38 times. In total, \~ 603 mL of blood will be drawn by experienced nurses over the entire RCT (>6 month period). During DEXA scans, participants will receive a total of about 0.006 mSv of radiation.
Invasive measurements that participants can experience as burden are collection of faecal and urine samples, and finding back the Simba capsules in the stool. Non-invasive measurements for participants are wearing the CGM, wearing the ActiGraph, consuming the blue cakes, and performing sensory tests.
Exclusion Criteria:
In this arm, participants will first receive the NNS diet, and the no-NNS diet in the second study period.
Other: Diet with non-nutritive sweeteners · Other: Diet without non-nutritive sweeteners
In this arm, participants will first receive the no-NNS diet, and the NNS diet in the second study period.
Other: Diet with non-nutritive sweeteners · Other: Diet without non-nutritive sweeteners
Fully controlled diet with added mixture of non-nutritive sweeteners. The mixture consist of 6 different non-nutritive sweeteners: acesulfame-K, aspartame, cyclamate, saccharin, sucralose, and rebaudioside A (stevia).
Fully controlled diet without any non-nutritive sweeteners added.
Difference in change in 2h iAUC glucose after 6 weeks between the intervention and the control.
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.
Time frame: Week 2 and week 8 in both intervention periods (4 times in total)
Matsuda index
Matsuda index after an OGTT
Time frame: Week 2 and week 8 in both intervention periods (4 times in total)
Fasting blood glucose
Fasting blood glucose
Time frame: Baseline & 2 times per intervention period (week 2 and week 8). 5 times in total.
Fasting blood insulin
Fasting blood insulin
Time frame: Baseline & 2 times per intervention period (week 2 and week 8). 5 times in total.
Postprandial insulin response
2-hour iAUC blood insulin during OGTT
Time frame: Week 2 and 8 in both intervention periods (4 times in total).
Postprandial glucose response after a breakfast
Postprandial blood glucose responses (PPGR) following specific meals measured by CGM.
Time frame: Week 7 in both study periods (2 times in total)
Blood lipid profile
All circulating blood lipids, including all cholesterol types, triglycerides, and free fatty acids (FFAs).
Time frame: Baseline & 2 times per intervention period (week 2 and week 8). 5 times in total.
Gut microbiota composition
Microbiota composition in faeces
Time frame: 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
Microbiota functionality measured in faeces
Time frame: 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
Microbial metabolites measured in faeces
Time frame: 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
Microbiota composition of the small intestine measured with Simba Capsules
Time frame: Week 7 of both intervention periods (2 times in total).
Gastro-intestinal transit time
Gastro-intestinal transit time measured with blue muffins.
Time frame: Baseline & week 7 of both intervention periods (3 times in total).
Oral microbiome composition & function
Oral microbiome composition \& function measured in saliva
Time frame: Baseline & 2 times per intervention period (week 2 and week 8). 5 times in total.
Postprandial GLP-1 secretion
3-hour AUC of GLP-1 during an OGTT.
Time frame: Week 2 and 8 of both intervention periods (4 times in total).
Postprandial GIP secretion
3-hour AUC of GIP during an OGTT.
Time frame: Week 2 and 8 of both intervention periods (4 times in total).
Sweetness-liker phenotype
Sweetness-liker phenotype, with the sweetness liker test.
Time frame: Baseline & 2 times per intervention period (week 2 and week 8). 5 times in total.
Sweetness preference & liking
Sweetness preference \& liking measured on a rank-rating scale. Preference will be determined using the categorical values from the rank-rating scale (1-5), and liking will be determined using the continuous values from the rank-rating scale (0-100).
Time frame: Baseline & 2 times per intervention period (week 2 and week 8). 5 times in total.
Sweet taste sensitivity
Sweet taste sensitivity measured on a 100mm Visual Analogue Scale. A higher score for all solutions indicates a higher sweet taste sensitivity.
Time frame: Baseline & 2 times per intervention period (week 2 and week 8). 5 times in total.
Excretion of NNS in urine
Excretion of NNS in urine
Time frame: 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
Excretion of NNS in saliva
Time frame: Baseline & 2 times per intervention period (week 2 and week 8). 5 times in total.
Anthropometrics
Measured as weight (kg), height (m), waist circumference (cm), and hip circumference (cm). Weight and height will be combined to report BMI in kg/m\^2.
Time frame: Baseline
Body composition
Body composition as measured by DEXA (Dual Energy X-ray Absorptiometry).
Time frame: Baseline & week 8 of both intervention periods (3 times in total).
Habitual food intake
Habitual dietary intake assessment with a food frequency questionnaire (FFQ).
Time frame: Baseline
Physical activity level
Physical activity level by the Short Questionnaire to Assess Health-enhancing physical activity (SQUASH).
Time frame: Baseline.
Habitual NNS consumption
Habitual NNS consumption by questionnaire
Time frame: Baseline
Gastro-intestinal symptoms
Gastro-intestinal symptoms by GSRS questionnaire.
Time frame: Once during the characterisation period (1 week), and every week during the first intervention period (8 weeks) and every week during the second intervention period (8 weeks). In total up to 17 weeks.
Satiety
Satiety questionnaire, adapted from the Control of Eating Questionnaire.
Time frame: Once during the characterisation period (1 week), and every week during the first intervention period (8 weeks) and every week during the second intervention period (8 weeks). In total up to 17 weeks.
Genetic variation
Single Nucleotide Polymorphisms (SNPs) in genes relevant collected using buffycoat.
Time frame: Baseline
Taste function
Measure the ability to recognize the basic tastes in different concentrations, assessed with validated Taste Strips.
Time frame: Baseline
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
No contact was published for this record. The registry link below has the sponsor’s details.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Wageningen University