Effects of Acute Ketone Supplementation on the Brain

NCT07711990 | Recruiting

• 1 other identifier: STUDY20251460
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine how a ketone ester supplement affects brain function, brain blood flow, and brain metabolism in healthy middle-aged and older adults. Ketones are naturally produced by the body during periods of fasting or carbohydrate restriction and serve as an alternative fuel source for the brain. Researchers are interested in whether increasing blood ketone levels through supplementation can alter brain activity and blood flow in ways that may support healthy brain function. Participants will consume a ketone ester supplement and a placebo in separate study visits. Brain imaging, blood measurements, and cognitive testing will be used to evaluate the effects of each intervention. Findings from this study will help researchers better understand how ketones influence the healthy aging brain and may provide preliminary data for future studies in populations at risk for cognitive decline.

Conditions

Brain Health

Keywords

ketone supplement; brain MRI; brain MRS

Outcome Measures

Primary Outcomes (11)

• Cerebral Blood Flow

  To detect a clinically meaningful difference in cerebral blood flow (CBF) between ketone ester and placebo conditions in healthy adults

  Acute response following 2-day lead in

• Brain Glutamate Concentration

  To detect a difference in brain glutamate concentration (mM) between ketone ester and placebo conditions in healthy adults, measured using proton magnetic resonance spectroscopy (1H-MRS).

  Acute response following 2-day lead in

• Brain GABA Concentration

  To detect a difference in brain gamma-aminobutyric acid (GABA) concentration (mM) between ketone ester and placebo conditions in healthy adults, measured using proton magnetic resonance spectroscopy (1H-MRS).

  Acute response following 2-day lead in

• Brain Lactate Concentration

  To detect a difference in brain lactate concentration (mM) between ketone ester and placebo conditions in healthy adults, measured using proton magnetic resonance spectroscopy (1H-MRS).

  Acute response following 2-day lead in

• Brain Choline Concentration

  To detect a difference in brain choline concentration (mM) between ketone ester and placebo conditions in healthy adults, measured using proton magnetic resonance spectroscopy (1H-MRS).

  Acute response following 2-day lead in

• Brain N-Acetylaspartate (NAA) Concentration

  To detect a difference in brain N-acetylaspartate (NAA) concentration (mM) between ketone ester and placebo conditions in healthy adults, measured using proton magnetic resonance spectroscopy (1H-MRS).

  Acute response following 2-day lead in

• Brain Glucose Concentration

  To detect a difference in brain glucose concentration (mM) between ketone ester and placebo conditions in healthy adults, measured using proton magnetic resonance spectroscopy (1H-MRS).

  Acute response following 2-day lead in

• Brain Beta-Hydroxybutyrate (BHB) Concentration

  To detect a difference in brain beta-hydroxybutyrate (BHB) concentration (mM) between ketone ester and placebo conditions in healthy adults, measured using proton magnetic resonance spectroscopy (1H-MRS).

  Acute response following 2-day lead in

• Functional Brain Connectivity

  Change in resting-state brain network connectivity measured using blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI).

  Acute response following 2-day lead in

• Brain Acetoacetate Concentration

  To detect a difference in brain acetoacetate concentration (mM) between ketone ester and placebo conditions in healthy adults, measured using proton magnetic resonance spectroscopy (1H-MRS).

  Acute response following 2-day lead in

• Brain Glutamine Concentration

  To detect a difference in brain glutamine concentration (mM) between ketone ester and placebo conditions in healthy adults, measured using proton magnetic resonance spectroscopy (1H-MRS).

  Acute response following 2-day lead in

Secondary Outcomes (3)

• Blood Ketone Concentration

  Acute response following 2-day lead in

• Blood Glucose Concentration

  Acute response following 2-day lead in

• Cognitive Performance (RBANS Total Scale Score)

  Acute response following 2-day lead in

Study Arms (2)

Ketone Supplement drink

ACTIVE COMPARATOR

Drink contains 25 g of C8 Diester , 50g consumed total per day using split dose

Dietary Supplement: Ketone Ester Drink

Placebo Drink

PLACEBO COMPARATOR

Drink contains no ketones, kcal and volume matched

Dietary Supplement: Placebo

Interventions

Ketone Ester Drink DIETARY_SUPPLEMENT

The ketone ester beverage contains 25 g of C8 Diester emulsified in a matrix of water, whey protein concentrate, modified gum acacia, natural and artificial flavors and cocoa powder. It contains 210 kcal, 0.5 g fat, 2 g carbohydrates, and 2 g protein. Dose consumed is 50 g, 2 times per day for 2 days. The placebo (PL) will be calorie and volume matched to the KE and be formulated with standard dietary ingredients.

Ketone Supplement drink

Placebo DIETARY_SUPPLEMENT

The placebo drink will be calorie and volume matched to the KE and be formulated with standard dietary ingredients.

Placebo Drink

Eligibility Criteria

• Age: 45 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥45 years and ≤65 years
• Able to comply with study requirements including presenting for each test session following an overnight fast and not following a ketogenic diet during the duration of the study.
• BMI between 18.5 and 30 kg/m2

You may not qualify if:

• Non-English Speaking
• Currently taking a ketone ester supplement, ketone salt supplement, or on a ketogenic diet
• Pregnancy, a urine pregnancy test will be given to all women before scanning to confirm nonpregnant status
• Currently breastfeeding
• Allergies to components in the test products, including milk protein, and not lactose intolerant
• History of high blood pressure
• History of alcoholism (previous 2 years)
• History of illicit drug use
• History of head trauma involving loss of consciousness or skull fracture
• Diagnosed neurological disease
• Taking psychiatric prescriptive medications (antipsychotics, antidepressants, or barbiturates) or over-the-counter (OTC) medications (other than those taken as nutritional supplements for non-therapeutic indications)
• Current smoker
• Currently consuming a habitual ketogenic diet, or was consuming a habitual ketogenic diet in the past three months
• Any condition or material in the body that is a contraindication for MRI procedures

Sponsors & Collaborators

• Christopher Crabtree: lead

Study Sites (1)

The Ohio State University

Columbus, Ohio, 43210, United States

RECRUITING

Central Study Contacts

Christopher Crabtree, Ph.D.

CONTACT

614-688-5623; Christopher.Crabtree@osumc.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Research Scientist

Model Details: This study uses a randomized, double-blind, placebo-controlled crossover design. Participants will complete two intervention periods in random order, receiving a ketone ester supplement during one period and a placebo during the other. Each intervention period includes a two-day supplementation lead-in followed by a testing visit. The two intervention periods are separated by a 3- to 7-day washout period. Investigators and participants will remain blinded to treatment assignment until study completion.

Study Record Dates

• First Submitted: July 13, 2026
• First Posted: July 17, 2026
• Study Start: June 15, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: July 17, 2026

Record last verified: 2026-07

Locations

US (1)