The goal of this observational study is to determine changes in brain activity and blood sugar in response to the ingestion of flavored waters sweetened with either the nutritive sugar sucrose or different low-caloric sweeteners in healthy normal-weight individuals aged between 18 and 30 years.

The main question it aims to answer is in how far brain and glycemic responses differ between a sugar-sweetened drink and drinks sweetened with different low-caloric sweeteners.

Participants will visit after an overnight fast six times and then have an MRI brain scan before and after consumption of 500 ml of one of the study drinks (beverage sweetened with sucrose or one of four non-caloric sweeteners, or water).

Rationale: The brain is crucial in the regulation of energy intake and maintaining homeostasis which is subserved by an interaction of homeostatic and reward-related brain areas. These brain areas integrate multiple neural and hormonal signals related to energy content such as sweet taste and food reward in the form of ingested energy. Sugar-sweetened soft drinks have been shown to contribute to overconsumption and obesity. Therefore, there is great consumer interest in drinks with low-caloric sweeteners because they do not contribute to energy intake while still providing the hedonic experience of sweet taste. However, different low-caloric sweeteners may have differential effects on the brain because of (subliminal) taste difference and their different metabolic fate. We hypothesize that the brain and glycemic responses to drinks sweetened with sugar and different low-caloric sweeteners will be different. This may have implications for their reward value.

Objective: To determine changes in brain activity in response to the ingestion of flavored waters sweetened with either the nutritive sugar sucrose or different low-caloric sweeteners.

Study design: Randomized crossover design with six treatments. Study population: 30 healthy, non-smoking, normal-weight individuals, aged between 18 and 30 years.

Intervention: Participants will be scanned using MRI before and after consumption of six 500-ml drinks: water; water + sucrose; water + sucralose; water + stevia extract; water + allulose + stevia; water + monk fruit extract. Regional cerebral blood flow (rCBF) and resting state functional MRI (rsfMRI) scans will be made at baseline and at t=5 and t=30 min. Additionally, gastric emptying of the drinks will be examined through gastric MRI at t=15, 25 and 45 min. Blood samples will be collected to measure changes in insulin and glucose levels at baseline and at t=5, 15, 30, 45 and 60 min for all sweet treatments. Participants will rate their appetite and thirst at baseline and at t=15, 25, 30, 45 and 60 min.

Inclusion Criteria:

• Age between 18 and 30 years
• BMI between 18.5 and 25 kg/m2
• Apparently healthy (self-reported)
• Right-handed (because brain responses may differ between right- and left handed individuals)
• Sufficient blood hemoglobin (Hb) levels (women > 7,5; men > 8.5 g/dl) and having antecubital veins suitable for blood sampling via a catheter
• Willing to comply with the study procedures
• Willing to be informed about incidental findings of pathology and consenting to informing their general practitioner about this.

Exclusion Criteria:

• Having disturbances of glucose metabolism such as being prediabetic or diabetic
• Use of medication that could influence study results including insulin/metformin/proton pump inhibitors, antacids, anti-depressants
• Allergy or intolerance for any of the study products/compounds (sucrose, sucralose, stevia extract, allulose, monk fruit extract)
• Being a regular smoker (smoking more than one cigarette or e-cigarette with nicotin per day)
• Drinking more than 14 glasses of alcohol a week
• Having genetic, psychiatric or neurological diseases affecting the brain
• Gastric disorders or regular gastric complaints (more than once per week), for example heart burn
• Having renal or hepatic disease
• Using recreational drugs more than once per week (e.g. marihuana, XTC, GHB, laughing gas)
• Having given a blood donation in the past two months
• Being pregnant, lactating or planning on becoming pregnant during the study
• Currently following or having followed calorie-restricted diet in the past two months
• Participating in other research during the study period
• Not having a general practitioner
• Being an employee or student of the Division of Human Nutrition and Health
• Having a contra-indication to MRI scanning

With the exception of the water treatment, treatment type will be blind for the participants and the researchers. The primary analysis will be performed completely blinded.