The Impact of the Physiological Response to Sugar on Brain Activity and Behavior

The goal of this pilot study is to test the feasibility of assessing how biological factors and chemical properties of sugars may influence metabolism and food reward in humans. The main questions it aims to answer are:

• Can differences in appetitive responses and neural activations to sucrose (table sugar) and its chemical components (glucose and fructose) be measured and quantified?

This study is a crossover design, meaning every participant will complete every condition. Participants will consume beverages containing sucrose, glucose, or fructose, which are each novelly flavored, 6 times within a week. During one of the consumption times, energy expenditure, carbohydrate oxidation, and blood glucose will be measured in the lab before and for 2 hours after consumption. After participants have consumed each condition, they will undergo a tasting task in the MRI scanner, neural responses to receipt of the beverages are measured.

Study Overview

• Status: Completed
• Conditions: Food Preferences; Appetitive Behavior
• Intervention / Treatment: Other: Sucrose drink; Other: Glucose drink; Other: Fructose drink

Detailed Description

Prior studies in humans indicate that while energy expenditure response is similar after consumption of equal amounts of fructose, glucose, and sucrose (a dimer of glucose + fructose), carbohydrate oxidation and blood glucose responses differ. Elevated carbohydrate oxidation responses appear to be driven by the presence of fructose, and elevated blood glucose responses appear to be driven by the presence of glucose. Prior work also suggests that post-ingestive signals of glucose availability, measure specifically as blood glucose levels, intestinal glucose transporter activity, and carbohydrate oxidation rate, are all associated with elevated brain response to calorie-predictive flavor cues and reward learning of these flavor cues. However, in animal models, glucose has been shown to repeatedly and reliably condition these calorie-predictive learning responses, but fructose does not. Human work has indicated that oxidation of glucose is critical for these responses. Thus, it is unclear what roles fructose and glucose each play in conditioning reward responses and flavor-calorie learning. We hypothesize that fructose plays a synergistic role in enhancing flavor-calorie learning without itself conditioning the reward response.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Roanoke, Virginia, United States, 24016
      • Fralin Biomedical Research Institute at Virginia Tech Carilion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. BMI between 18.5-25 kg/m2
2. Not pregnant or planning to become pregnant during study participation
3. Residing in the Roanoke area and/or willing/able to attend sessions at the Fralin Biomedical Research Institute (FBRI) at Virginia Tech Carilion
4. Weigh at least 110 lbs

Exclusion Criteria:

1. Current inhaled nicotine use
2. History of alcohol dependence.
3. Current or past diagnosis of cardiometabolic disease or problems, including diabetes, endocrine, heart, or thyroid problems, that may influence study outcomes
4. Hemoglobin A1C >5.7%
5. Taking medications known to influence study measures (including attention-deficit/hyperactivity disorder (ADHD), allergy, antidepressant, antipsychotic, anxiolytic, birth control, blood pressure, blood glucose, cholesterol, thyroid, sleep, or weight loss medications)
6. Active medical or neurologic disorder, including cardiometabolic conditions or gastrointestinal conditions that may influence study outcomes
7. Recent change in body weight (gain or loss of > 5 lbs within the past 3 months)
8. Current shift work (typical pattern of work/activity overnight)
9. Previous weight loss surgery
10. Adherence to a special diet within the past 3 months (e.g., low-carb or ketogenic diet, exclusion of food groups/specific macronutrients, intermittent fasting, etc.)
11. Allergy to any food or ingredient included in the study diets, meals, or beverages
12. Currently pregnant or planning to become pregnant during study participation
13. Claustrophobia
14. Contraindications for MRI, including pacemaker, aneurysm clips, neurostimulators, cochlear or other implants, metal in eyes, regular work with steel, etc. (Note: This is an fMRI-specific exclusion criterion. Participants may be allowed to participate in all other study sessions and measures that do not involve fMRI.)
15. Contraindications for bioelectrical impedance analysis, specifically implanted devices
16. Use of substances (or combinations of substances) in doses and frequencies that could influence neural outcomes of study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sucrose, then Glucose, then Fructose; Participants will consume a 110 kcal sucrose drink 6 times during 1 week. Then, they will consume a 110 kcal glucose drink 6 times during 1 week, and then, a 110 kcal fructose drink 6 times during 1 week.	Other: Sucrose drink; Participants will consume flavored beverage solutions containing 110 calories of sucrose in 6 exposure sessions within 1 week. One exposure session will include pre- and post-consumption blood draws and indirect calorimetry measurements inside a metabolic chamber over a 2-hour period. The other 5 exposure sessions will occur at specified times outside the laboratory sessions. Subjective ratings of internal state (i.e., hunger, fullness, and thirst) will be collected throughout each exposure. Subjective ratings of liking and wanting of each beverage will also be assessed.; Other Names: Flavored beverage solution with 110 calories of sucrose; Other: Glucose drink; Participants will consume flavored beverage solutions containing 110 calories of glucose in 6 exposure sessions within 1 week. One exposure session will include pre- and post-consumption blood draws and indirect calorimetry measurements inside a metabolic chamber over a 2-hour period. The other 5 exposure sessions will occur at specified times outside the laboratory sessions. Subjective ratings of internal state (i.e., hunger, fullness, and thirst) will be collected throughout each exposure. Subjective ratings of liking and wanting of each beverage will also be assessed.; Other Names: Flavored beverage solution with 110 calories of glucose; Other: Fructose drink; Participants will consume flavored beverage solutions containing 110 calories of fructose in 6 exposure sessions within 1 week. One exposure session will include pre- and post-consumption blood draws and indirect calorimetry measurements inside a metabolic chamber over a 2-hour period. The other 5 exposure sessions will occur at specified times outside the laboratory sessions. Subjective ratings of internal state (i.e., hunger, fullness, and thirst) will be collected throughout each exposure. Subjective ratings of liking and wanting of each beverage will also be assessed.; Other Names: Flavored beverage solution with 110 calories of fructose
Experimental: Sucrose, then Fructose, then Glucose; Participants will consume a 110 kcal sucrose drink 6 times during 1 week. Then, they will consume a 110 kcal fructose drink 6 times during 1 week, and then, a 110 kcal glucose drink 6 times during 1 week.	Other: Sucrose drink; Participants will consume flavored beverage solutions containing 110 calories of sucrose in 6 exposure sessions within 1 week. One exposure session will include pre- and post-consumption blood draws and indirect calorimetry measurements inside a metabolic chamber over a 2-hour period. The other 5 exposure sessions will occur at specified times outside the laboratory sessions. Subjective ratings of internal state (i.e., hunger, fullness, and thirst) will be collected throughout each exposure. Subjective ratings of liking and wanting of each beverage will also be assessed.; Other Names: Flavored beverage solution with 110 calories of sucrose; Other: Glucose drink; Participants will consume flavored beverage solutions containing 110 calories of glucose in 6 exposure sessions within 1 week. One exposure session will include pre- and post-consumption blood draws and indirect calorimetry measurements inside a metabolic chamber over a 2-hour period. The other 5 exposure sessions will occur at specified times outside the laboratory sessions. Subjective ratings of internal state (i.e., hunger, fullness, and thirst) will be collected throughout each exposure. Subjective ratings of liking and wanting of each beverage will also be assessed.; Other Names: Flavored beverage solution with 110 calories of glucose; Other: Fructose drink; Participants will consume flavored beverage solutions containing 110 calories of fructose in 6 exposure sessions within 1 week. One exposure session will include pre- and post-consumption blood draws and indirect calorimetry measurements inside a metabolic chamber over a 2-hour period. The other 5 exposure sessions will occur at specified times outside the laboratory sessions. Subjective ratings of internal state (i.e., hunger, fullness, and thirst) will be collected throughout each exposure. Subjective ratings of liking and wanting of each beverage will also be assessed.; Other Names: Flavored beverage solution with 110 calories of fructose
Experimental: Glucose, then Fructose, then Sucrose; Participants will consume a 110 kcal glucose drink 6 times during 1 week. Then, they will consume a 110 kcal fructose drink 6 times during 1 week, and then, a 110 kcal sucrose drink 6 times during 1 week.	Other: Sucrose drink; Participants will consume flavored beverage solutions containing 110 calories of sucrose in 6 exposure sessions within 1 week. One exposure session will include pre- and post-consumption blood draws and indirect calorimetry measurements inside a metabolic chamber over a 2-hour period. The other 5 exposure sessions will occur at specified times outside the laboratory sessions. Subjective ratings of internal state (i.e., hunger, fullness, and thirst) will be collected throughout each exposure. Subjective ratings of liking and wanting of each beverage will also be assessed.; Other Names: Flavored beverage solution with 110 calories of sucrose; Other: Glucose drink; Participants will consume flavored beverage solutions containing 110 calories of glucose in 6 exposure sessions within 1 week. One exposure session will include pre- and post-consumption blood draws and indirect calorimetry measurements inside a metabolic chamber over a 2-hour period. The other 5 exposure sessions will occur at specified times outside the laboratory sessions. Subjective ratings of internal state (i.e., hunger, fullness, and thirst) will be collected throughout each exposure. Subjective ratings of liking and wanting of each beverage will also be assessed.; Other Names: Flavored beverage solution with 110 calories of glucose; Other: Fructose drink; Participants will consume flavored beverage solutions containing 110 calories of fructose in 6 exposure sessions within 1 week. One exposure session will include pre- and post-consumption blood draws and indirect calorimetry measurements inside a metabolic chamber over a 2-hour period. The other 5 exposure sessions will occur at specified times outside the laboratory sessions. Subjective ratings of internal state (i.e., hunger, fullness, and thirst) will be collected throughout each exposure. Subjective ratings of liking and wanting of each beverage will also be assessed.; Other Names: Flavored beverage solution with 110 calories of fructose
Experimental: Glucose, then Sucrose, then Fructose; Participants will consume a 110 kcal glucose drink 6 times during 1 week. Then, they will consume a 110 kcal sucrose drink 6 times during 1 week, and then, a 110 kcal fructose drink 6 times during 1 week.	Other: Sucrose drink; Participants will consume flavored beverage solutions containing 110 calories of sucrose in 6 exposure sessions within 1 week. One exposure session will include pre- and post-consumption blood draws and indirect calorimetry measurements inside a metabolic chamber over a 2-hour period. The other 5 exposure sessions will occur at specified times outside the laboratory sessions. Subjective ratings of internal state (i.e., hunger, fullness, and thirst) will be collected throughout each exposure. Subjective ratings of liking and wanting of each beverage will also be assessed.; Other Names: Flavored beverage solution with 110 calories of sucrose; Other: Glucose drink; Participants will consume flavored beverage solutions containing 110 calories of glucose in 6 exposure sessions within 1 week. One exposure session will include pre- and post-consumption blood draws and indirect calorimetry measurements inside a metabolic chamber over a 2-hour period. The other 5 exposure sessions will occur at specified times outside the laboratory sessions. Subjective ratings of internal state (i.e., hunger, fullness, and thirst) will be collected throughout each exposure. Subjective ratings of liking and wanting of each beverage will also be assessed.; Other Names: Flavored beverage solution with 110 calories of glucose; Other: Fructose drink; Participants will consume flavored beverage solutions containing 110 calories of fructose in 6 exposure sessions within 1 week. One exposure session will include pre- and post-consumption blood draws and indirect calorimetry measurements inside a metabolic chamber over a 2-hour period. The other 5 exposure sessions will occur at specified times outside the laboratory sessions. Subjective ratings of internal state (i.e., hunger, fullness, and thirst) will be collected throughout each exposure. Subjective ratings of liking and wanting of each beverage will also be assessed.; Other Names: Flavored beverage solution with 110 calories of fructose
Experimental: Fructose, then Glucose, then Sucrose; Participants will consume a 110 kcal fructose drink 6 times during 1 week. Then, they will consume a 110 kcal glucose drink 6 times during 1 week, and then, a 110 kcal sucrose drink 6 times during 1 week.	Other: Sucrose drink; Participants will consume flavored beverage solutions containing 110 calories of sucrose in 6 exposure sessions within 1 week. One exposure session will include pre- and post-consumption blood draws and indirect calorimetry measurements inside a metabolic chamber over a 2-hour period. The other 5 exposure sessions will occur at specified times outside the laboratory sessions. Subjective ratings of internal state (i.e., hunger, fullness, and thirst) will be collected throughout each exposure. Subjective ratings of liking and wanting of each beverage will also be assessed.; Other Names: Flavored beverage solution with 110 calories of sucrose; Other: Glucose drink; Participants will consume flavored beverage solutions containing 110 calories of glucose in 6 exposure sessions within 1 week. One exposure session will include pre- and post-consumption blood draws and indirect calorimetry measurements inside a metabolic chamber over a 2-hour period. The other 5 exposure sessions will occur at specified times outside the laboratory sessions. Subjective ratings of internal state (i.e., hunger, fullness, and thirst) will be collected throughout each exposure. Subjective ratings of liking and wanting of each beverage will also be assessed.; Other Names: Flavored beverage solution with 110 calories of glucose; Other: Fructose drink; Participants will consume flavored beverage solutions containing 110 calories of fructose in 6 exposure sessions within 1 week. One exposure session will include pre- and post-consumption blood draws and indirect calorimetry measurements inside a metabolic chamber over a 2-hour period. The other 5 exposure sessions will occur at specified times outside the laboratory sessions. Subjective ratings of internal state (i.e., hunger, fullness, and thirst) will be collected throughout each exposure. Subjective ratings of liking and wanting of each beverage will also be assessed.; Other Names: Flavored beverage solution with 110 calories of fructose
Experimental: Fructose, then Sucrose, then Glucose; Participants will consume a 110 kcal fructose drink 6 times during 1 week. Then, they will consume a 110 kcal sucrose drink 6 times during 1 week, and then, a 110 kcal glucose drink 6 times during 1 week.	Other: Sucrose drink; Participants will consume flavored beverage solutions containing 110 calories of sucrose in 6 exposure sessions within 1 week. One exposure session will include pre- and post-consumption blood draws and indirect calorimetry measurements inside a metabolic chamber over a 2-hour period. The other 5 exposure sessions will occur at specified times outside the laboratory sessions. Subjective ratings of internal state (i.e., hunger, fullness, and thirst) will be collected throughout each exposure. Subjective ratings of liking and wanting of each beverage will also be assessed.; Other Names: Flavored beverage solution with 110 calories of sucrose; Other: Glucose drink; Participants will consume flavored beverage solutions containing 110 calories of glucose in 6 exposure sessions within 1 week. One exposure session will include pre- and post-consumption blood draws and indirect calorimetry measurements inside a metabolic chamber over a 2-hour period. The other 5 exposure sessions will occur at specified times outside the laboratory sessions. Subjective ratings of internal state (i.e., hunger, fullness, and thirst) will be collected throughout each exposure. Subjective ratings of liking and wanting of each beverage will also be assessed.; Other Names: Flavored beverage solution with 110 calories of glucose; Other: Fructose drink; Participants will consume flavored beverage solutions containing 110 calories of fructose in 6 exposure sessions within 1 week. One exposure session will include pre- and post-consumption blood draws and indirect calorimetry measurements inside a metabolic chamber over a 2-hour period. The other 5 exposure sessions will occur at specified times outside the laboratory sessions. Subjective ratings of internal state (i.e., hunger, fullness, and thirst) will be collected throughout each exposure. Subjective ratings of liking and wanting of each beverage will also be assessed.; Other Names: Flavored beverage solution with 110 calories of fructose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Preference- Subjective Liking Ratings for Each Beverage on a Scale	Subjective ratings of liking of flavors used in the intervention will be assessed at baseline and after the intervention. The generalized Labeled Magnitude Scale will be used. The scale is anchored by descriptors of "Most Disliked Sensation Imaginable" and "Most Liked Sensation Imaginable" at the lower and upper ends, respectively. The score is determined by the place on the scale participants select (range of scale is 0-100). An increase in score from baseline to post-intervention indicates an increase in liking.	Immediately after informed consent and in the post-test session approximately 5 weeks later

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-Test Measure of Preference- Subjective Wanting Ratings for Each Beverage on a Scale	Subjective ratings of liking of flavors used in the intervention will be assessed at baseline and after the intervention. A Visual Analog Scale will be used. Participants select a place on the line that corresponds with their subjective rating, and the score is determined by the place selected (range of scores is 0-100). The line is anchored by polar opposite descriptors ("Do not want at all" and "Want very much"). An increase in score from baseline to post-intervention indicates and increase in wanting.	At the end of study; approximately 5 weeks after first session
Post-Test Measure of Preference - Wanting (ad Libitum Intake): The Amount Consumed of Each Beverage is Reported as the Outcome	Ad libitum intake will be used as a measure of wanting in a post-test session. Participants will be provided each beverage used during the intervention and asked to drink as much or as little of them as they would like over a 30-minute period.	At the end of study; approximately 5 weeks after first session
Post-Test Measure of Preference- Wanting (Forced Choice): Number of Participants Who Chose Each Indicated Beverage	Forced choice will be used as a measure of wanting in a post-test session. Participants will be provided each of the beverages used during the intervention and asked to choose 1 to take home with them.	At the end of study; approximately 5 weeks after first session
Blood Oxygen Level-dependent (BOLD) Response to Beverages	In a post-test session, functional magnetic resonance imaging (fMRI) scans were performed while beverages (without calories) used during the intervention and a tasteless solution are delivered through a custom manifold fitted to a head coil and connected to a pump system that allows precisely timed and measured delivery of liquids. Participants receive the glucose, sucrose, fructose, and tasteless (control) solutions 18 times each over the course of 2 runs. Contrasts of interest are the blood oxygen level-dependent (BOLD) response of glucose+>tasteless solution, sucrose>tasteless solution, and fructose>tasteless deliveries. Parameter estimates for these contrasts are extracted and reported. A positive outcome reflects greater whole-brain BOLD response for the sugar condition compared with a tasteless solution.	At the end of study; approximately 5 weeks after first session
Blood Glucose Response to Beverages	Blood glucose will be assessed at baseline and at set time points for 2 hours after consumption of intervention beverages (baseline, 5-, 20-, 40-, 60-, 90-, and 120-minutes after drink consumption)in one exposure session. Area under the curve is calculated using these time points and reported as the outcome measure.	Each week for 3 weeks during the study
Energy Expenditure in Response to Beverages	Indirect calorimetry will be used to determine energy expenditure at baseline and for 120 minutes after consumption of condition beverages in an exposure session. Area under the curve is calculated as a change from baseline energy expenditure using minute-by-minute resolution across 120 minutes and reported as the outcome measure.	Each week for 3 weeks during the study

Collaborators and Investigators

• Sponsor: Virginia Polytechnic Institute and State University

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2023
• Primary Completion (Actual): July 22, 2024
• Study Completion (Actual): July 22, 2024

Study Registration Dates

• First Submitted: May 3, 2023
• First Submitted That Met QC Criteria: August 24, 2023
• First Posted (Actual): August 29, 2023

Study Record Updates

• Last Update Posted (Estimated): September 11, 2025
• Last Update Submitted That Met QC Criteria: August 21, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavior; Behavior, Animal; Feeding Behavior; Appetitive Behavior; Food Preferences; Pharmaceutical Solutions
• Other Study ID Numbers: #23-297

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No