The Effects of Exogenous Ketones on Cognitive Function

The University of Alabama at Birmingham

Status: Enrolling

Conditions: Ketone Monoester; Placebo - Control

Treatments: Dietary Supplement: Placebo; Dietary Supplement: Ketone Monoester (KE)

Study type: Interventional

Funder types: Other

Identifiers

NCT07051655

IRB-300013940

UAB (Other Grant/Funding Number)

Details and patient eligibility

About

The purpose of this study is to evaluate the acute effects of exogenous ketone monoester (KME) supplementation on cognitive function in three groups of adults aged 19-55 years: (1) obese, sedentary individuals; (2) lean, sedentary individuals; and (3) lean individuals who engage in regular physical activity (e.g., collegiate or amateur athletes). The main questions it aims to answer are to:

• Assess the effects of acute KME supplementation versus placebo on cognitive, sensorimotor, and functional outcomes within groups.
• Compare cognitive performance across the three groups.

The primary outcome is cognitive performance assessed using the NIH Toolbox Cognition Battery. Secondary Outcomes include sensorimotor performance, measured using the Senaptec Sensory System, and driving performance, assessed with a driving simulator.

Full description

The purpose of this study is to evaluate the acute effects of exogenous ketone monoester (KME) supplementation on cognitive function in three groups of adults aged 19-55 years: (1) obese, sedentary individuals; (2) lean, sedentary individuals; and (3) lean individuals who engage in regular physical activity (e.g., collegiate or amateur athletes).

Exogenous ketones are considered a functional food, providing potential health benefits beyond basic nutrition. Specifically, KME has been shown to elevate circulating β-hydroxybutyrate (βHB), an alternative brain fuel that may enhance cognitive performance. Prior studies have demonstrated that KME improves cognition in individuals with Alzheimer's disease and mild cognitive impairment; however, its effects in otherwise healthy, sedentary individuals-particularly those with obesity-or in physically active individuals remain unknown.

Emerging evidence suggests that individuals with obesity may exhibit early cognitive deficits, especially in executive function and processing speed, which could increase their risk of accelerated cognitive decline with aging. These deficits may be partially attributed to impaired cerebral glucose metabolism. Since ketones serve as an efficient alternative energy substrate for the brain, ketone supplementation may help compensate for these metabolic deficits and enhance cognitive performance.

This study aims to compare cognitive performance across the three groups and assess the effects of acute KME supplementation versus placebo on cognitive, sensorimotor, and functional outcomes. The primary outcome is cognitive performance assessed using the NIH Toolbox Cognition Battery. Secondary Outcomes include sensorimotor performance, measured using the Senaptec Sensory System, and driving performance, assessed with a driving simulator.

This three-group design allows for the investigation of differential responses to ketone supplementation across a spectrum of metabolic health and physical conditioning. By using sensitive, multimodal assessment tools, this study will help determine whether exogenous ketones confer cognitive and functional benefits broadly, or whether these effects are most pronounced in metabolically impaired populations.

Enrollment: 45 estimated patients

Sex: All

Ages: 19 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Age 19-55 years
• BMI 30-40 (obese group) or 18-25 (lean and athlete groups)
• Sedentary status (<2 hrs/week of structured physical activity) for obese and lean groups
• Active athlete status (≥5 days/week of structured activity) for athlete group

Exclusion criteria

• Diagnosed neurological conditions (e.g., Parkinson's disease, multiple sclerosis, schizophrenia, muscular dystrophy, stroke, cerebral palsy)
• History of seizures
• Use of medications for diabetes, mood disorders, or attention disorders
• Pregnant or breastfeeding
• Current or recent use (within 1 month) of exogenous ketone supplements or adherence to a ketogenic diet

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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45 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Participants will undergo two test days (Test Day 1 and Test Day 2) separated by 3-7 days. On one test day, participants will consume a single dose of placebo (357 mg/kg of body weight). Thirty minutes after consuming the placebo, cognitive assessments will be completed including NIH Toolbox cognitive assessments, Senaptec Sensory Station, and driving simulation.

Treatment:

Dietary Supplement: Placebo

ketone monoester (KME)

Experimental group

Description:

Participants will undergo two test days separated by 3-7 days. On one test day, participants will consume a single dose of ketone monoester (KME) (357 mg/kg of body weight). Thirty minutes after consuming the KME, cognitive assessments will be completed including NIH Toolbox cognitive assessments, Senaptec Sensory Station, and driving simulation.

Treatment:

Dietary Supplement: Ketone Monoester (KE)