Neural and Metabolic Factors in Carbohydrate Reward

Official title

Neural and Metabolic Factors in Carbohydrate Reward: An Examination of Speed

Overview

Dietary factors contributed to nearly 50% of all cardiometabolic deaths in the US in 2012, making it one of the leading causes of preventable death in the US, second only to tobacco use. Human diets and food choices can't help but be influenced by the ubiquitous availability of processed foods of high-energy density and low nutrient content, consumption of which can lead to obesity, type II diabetes, heart disease, and other types of metabolic dysfunction. Surprisingly, food reinforcement does not rely on perceived energy density. Rather food reinforcement is associated with actual energy density and therefore, on an implicit knowledge of caloric content. That implicit knowledge must have a neural signature and a mechanism by which the gut communicates nutritive value to the brain. There is evidence, at least for fat and carbohydrates, that these pathways are separable, but terminate in a common neural structure, the dorsal striatum or caudate. This could be one mechanism by which modern processed foods high in both fat and carbohydrate are so sought after and readily consumed, In fact, when experimentally tested, fat and carbohydrate combinations were more reinforcing calorie for calorie than fat or carbohydrates alone and the level of reinforcement correlated with activity in reward- related brain areas. Beyond simple reinforcing value, it is known from the literature on drugs of abuse that the faster a drug is arrives at the brain, the higher it's abuse potential, however, little is known about how the kinetics of nutrient excursion influence food preference, choice, and brain activity. This project aims to test this specifically for carbohydrate reward.

Interventions

• Other CS- Beverage
  Conditioned Stimulus - (CS-): Flavored beverage solution with sweetness-matched sucralose. Participants will consume flavored beverage solutions sweetened with sucralose to match the sweetness of 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 measurement over a 2-hour period. The other 4 exposure sessions will occur at specified times outside the laboratory sessions. Subjective ratings
• Other CS+Fast
  (CS+): Flavored beverage solution with 110 calories of sucrose. 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 measurement over a 2-hour period. The other 4 exposure sessions will occur at specified times outside the laboratory sessions. Subjective ratings of internal state (i.e., hunger, fullness, and thirst) will be col
• Other CS+Slow
  (CS+): Flavored beverage solution with 110 calories of maltodextrin. Participants will consume flavored beverage solutions containing 110 calories of maltodexrin in 6 exposure sessions within 1 week.One exposure session will include pre- and post-consumption blood draws and indirect calorimetry measurement over a 2-hour period. The other 4 exposure sessions will occur at specified times outside the laboratory sessions. Subjective ratings of internal state (i.e., hunger, fullness, and thirst) wil

Primary outcome measures

• Change in preference- liking [Time frame: at the end of the study; 5 weeks after start of study]

Secondary outcome measures (9)

• Change in preference- wanting, rated [Time frame: at the end of the study; 5 weeks after start of study]
• Change in preference- wanting, ad lib intake [Time frame: at the end of the study; 5 weeks after start of study]
• Change in preference- wanting, forced choice [Time frame: at the end of the study; 5 weeks after start of study]
• Blood oxygen level-dependent (BOLD) response to beverages [Time frame: at the end of the study; 5 weeks after start of study]
• Blood glucose response to beverages [Time frame: Each week for 3 weeks during the study]
• Blood insulin response to beverages [Time frame: Each week for 3 weeks during the study]
• Energy expenditure in response to beverages [Time frame: Each week for 3 weeks during the study]
• Respiratory exchange ratio in response to beverages [Time frame: Each week for 3 weeks during the study]
• Substrate oxidation in response to beverages [Time frame: Each week for 3 weeks during the study]

Eligibility criteria

Inclusion criteria

• BMI between 18.5-30 kg/m2
• Not pregnant or planning to become pregnant during study participation
• Residing in the Roanoke area and/or willing/able to attend sessions at the Fralin Biomedical Research Institute
• Able to speak and write in English

Exclusion criteria

• Current inhaled nicotine use
• History of alcohol dependence.
• Current or past diagnosis of diabetes or thyroid problems.
• Taking medications known to influence study measures (including antiglycemic agents, thyroid medications, sleep medications)
• Active medical or neurologic disorder.
• Current shift work (typical pattern of work/activity overnight)
• Previous weight loss surgery
• 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.)
• Allergy to any food or ingredient included in the study diets, meals, or beverages
• Currently pregnant or planning to become pregnant during study participation
• Claustrophobia
• Contraindications for MRI, including pacemaker, aneurysm clips, neurostimulators, cochlear or other implants, metal in eyes, regular work with steel, etc.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Crossover

Masking

Single blind

Primary purpose

Basic science

Study locations

United States · 1 center

• Fralin Biomedical Research Institute at VTC — Roanoke

Publications

• Kelly AL, Baugh ME, Ahrens ML, Valle AN, Sullivan RM, Oster ME, Fowler ME, Carter BE, Davy BM, Hanlon AL, DiFeliceantonio AG. Neural and metabolic factors in carbohydrate reward: Rationale, design, and methods for a flavor-nutrient learning paradigm in humans. Contemp Clin Trials. 2024 Dec;147:107717. doi: 10.1016/j.cct.2024.107717. Epub 2024 Oct 15. PMID 39413990

Identifiers

NCT: NCT06053294 · 19-927

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗