How non-nutritive sweeteners change blood sugar and gut health

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

We will test if using non-nutritive sweeteners instead of added sugars changes blood sugar control and gut markers in healthy adults aged 45–79.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 45 Years to 79 Years
• Sex: All
• Sponsor: Wageningen University (Academic / other)
• Drugs / interventions: radiation
• Locations: 1 site (Wageningen, Gelderland)
• Trial ID: NCT07361406 on ClinicalTrials.gov

What this trial studies

This is a single-blind, fully controlled dietary crossover where 60 healthy adults (age 45–79, BMI 20–35) follow two 8-week diets with a >6-week washout between them: one diet with added non-nutritive sweeteners (NNS) and one without. Diets are matched to reflect real-life NNS mixtures and doses and include a 2-week run-in followed by 6 weeks of intervention per period. The primary outcome is the within-person difference in blood glucose incremental area under the curve after a 75 g glucose load; secondary outcomes include changes in gut microbiome composition, gut hormone secretion, sweet taste sensitivity and preference, and urinary excretion of NNS. The controlled design aims to isolate effects of NNS on glucose regulation and gut-related measures under realistic intake conditions.

Who should consider this trial

Good fit: Ideal candidates are healthy adults aged 45–79 with BMI 20–35 who are not diabetic, can comply with in-person study visits and a fully controlled diet, and have veins suitable for catheter placement.

Not a fit: People with diagnosed type 1 or type 2 diabetes, recent antibiotic use, major gastrointestinal/liver/kidney disease, or those unable to follow the controlled dietary protocol are unlikely to benefit from this study.

Why it matters

Potential benefit: If successful, the results could clarify whether swapping sugar for non-nutritive sweeteners helps maintain better blood sugar control and preserves gut health, informing dietary guidance.

How similar studies have performed: Previous small or short-term human and animal studies have shown mixed results—some report NNS-related changes in glucose responses or the gut microbiome while others do not—so longer, fully controlled crossover data are still limited.

Eligibility criteria

Inclusion Criteria:

* Age 45-79 years;
* BMI of 20-35 kg/m2;
* Having veins suitable for placement of a venflon catheter.

Exclusion Criteria:

* 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.

Where this trial is running

Wageningen, Gelderland

• Wageningen University & Research — Wageningen, Gelderland, Netherlands (Recruiting)

Conditions Healthy Adult; glucose metabolism; gut microbiome; gut hormones; non-nutritive sweeteners