Can Exogenous Ketone Supplementation Compensate for Glucose Hypometabolism and Improve Cognitive Processing Speed in Veterans With Prediabetes?

University of Alabama at Birmingham

Summary

Brief Summary The goal of this clinical trial is to learn whether older adults with prediabetes, but no diagnosed cognitive impairment, show early changes in brain energy use and thinking speed compared to older adults with normal blood sugar levels. The study will also test whether a single dose of an exogenous ketone supplement can improve brain energy use and cognitive processing speed. The main questions it aims to answer are: Do older adults with prediabetes have lower brain glucose uptake and slower cognitive processing speed compared to those with normal glucose levels? Does a single dose of an exogenous ketone monoester supplement improve cognitive processing speed and brain glucose uptake? Researchers will compare older adults with prediabetes to older adults with normal glucose levels to determine whether differences exist in brain glucose metabolism and cognitive performance. In a subset of participants, researchers will also compare brain and cognitive outcomes before and after consuming a ketone monoester supplement (DeltaG, Oxford, England). Participants will: Complete metabolic testing to determine glucose status Undergo brain imaging using fluorodeoxyglucose positron emission tomography combined with magnetic resonance imaging (18FDG-PET/MRI) while performing a cognitive processing speed task Consume a single dose of a commercially available ketone monoester supplement during one study visit Complete cognitive testing during imaging to measure processing speed and brain activity The results of this study will help determine whether early metabolic dysfunction is linked to reduced brain energy use and whether ketones can temporarily support brain function in individuals at risk for dementia.

Description

Metabolic dysfunction and impaired brain energy metabolism are increasingly recognized as early contributors to cognitive decline and dementia risk. Type 2 diabetes is a well-established risk factor for cognitive impairment; however, less is known about whether cerebral metabolic alterations are already present during the prediabetes stage, prior to clinically apparent cognitive symptoms. Prediabetes is characterized by impaired glucose regulation and early insulin resistance, both of which may reduce the efficiency of glucose transport and utilization in the brain. Because glucose is the brai…

Eligibility

Age range: 60–75 years
Sex: All
Healthy volunteers: Yes

Detailed criteria

Inclusion Criteria: * Age 60 to 75 years * Able to provide written informed consent * Fluent in English * No diagnosed cognitive impairment or dementia Classified as either: * Prediabetes (based on American Diabetes Association criteria), or Normal glucose regulation (control group) * Medically stable and cleared to undergo positron emission tomography and magnetic resonance imaging * Willing to comply with study procedures, including metabolic testing, supplement ingestion, and neuroimaging Exclusion Criteria: * Diagnosis of mild cognitive impairment, dementia, or other neurodegenerative…

Interventions

Dietary Supplement
Ketone Monoester (KE)
The intervention is a single acute oral dose of a commercially available ketone monoester supplement (DeltaG®, Oxford, England). The active ingredient, (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, is rapidly metabolized after ingestion to raise circulating beta-hydroxybutyrate concentrations without requiring dietary carbohydrate restriction or fasting. The supplement is administered under supervised conditions during a study visit. Brain imaging with fluorodeoxyglucose F18 positron emission tomography combined with magnetic resonance imaging is performed during the post-ingestion period while participants complete a cognitive processing speed task. This protocol evaluates the immediate metabolic and neurocognitive effects of exogenous ketone administration within a single session.
Dietary Supplement
Placebo
The placebo consists of a taste-, color-, and volume-matched beverage formulated to mimic the sensory characteristics of the ketone monoester supplement but containing no active ketone ingredient. The placebo does not contain (R)-3-hydroxybutyl (R)-3-hydroxybutyrate) and does not elevate circulating beta-hydroxybutyrate concentrations. The placebo beverage will be administered orally under supervised research conditions during a study visit using procedures identical to the active supplement condition. Brain imaging with fluorodeoxyglucose F18 positron emission tomography combined with magnetic resonance imaging will be performed during the post-ingestion period while participants complete a cognitive processing speed task. This control condition allows isolation of the metabolic effects of ketone elevation from expectancy or beverage-related effects.

Locations (2)

UAB Comprehensive Cancer Center
Birmingham, Alabama
sksweatt@uab.edu 205-975-5398
Webb Nutrition Sciences Building
Birmingham, Alabama
sksweatt@uab.edu 205-975-5398

Summary

Description

Eligibility

Age range

60–75 years

Sex

All

Healthy volunteers

Yes

Detailed criteria

Interventions

Dietary Supplement

Ketone Monoester (KE)

The intervention is a single acute oral dose of a commercially available ketone monoester supplement (DeltaG®, Oxford, England). The active ingredient, (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, is rapidly metabolized after ingestion to raise circulating beta-hydroxybutyrate concentrations without requiring dietary carbohydrate restriction or fasting. The supplement is administered under supervised conditions during a study visit. Brain imaging with fluorodeoxyglucose F18 positron emission tomography combined with magnetic resonance imaging is performed during the post-ingestion period while participants complete a cognitive processing speed task. This protocol evaluates the immediate metabolic and neurocognitive effects of exogenous ketone administration within a single session.

Dietary Supplement

Placebo

The placebo consists of a taste-, color-, and volume-matched beverage formulated to mimic the sensory characteristics of the ketone monoester supplement but containing no active ketone ingredient. The placebo does not contain (R)-3-hydroxybutyl (R)-3-hydroxybutyrate) and does not elevate circulating beta-hydroxybutyrate concentrations. The placebo beverage will be administered orally under supervised research conditions during a study visit using procedures identical to the active supplement condition. Brain imaging with fluorodeoxyglucose F18 positron emission tomography combined with magnetic resonance imaging will be performed during the post-ingestion period while participants complete a cognitive processing speed task. This control condition allows isolation of the metabolic effects of ketone elevation from expectancy or beverage-related effects.