Ketone Supplements for Cognitive Impairment

Overseen By Walsh

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: McMaster University

Must not be taking: Ketogenic supplements

Disqualifiers: Mild cognitive impairment, Dementia, Cardiometabolic disease, Obesity, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a ketone supplement (ketone monoester, KME) can improve brain function in older adults who notice a decline in memory sharpness. The researchers aim to determine if this supplement boosts blood flow in the brain and enhances its connections. Participants will take both the ketone supplement and a placebo (a non-active substance) for 14 days each, with a break in between. This trial suits seniors who feel their memory is slipping but can still live independently and move around on their own. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are currently following a ketogenic diet or taking ketogenic supplements, you would not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that ketone monoester (KME) supplements are safe and generally easy to take. Studies have found that KME supplements can induce ketosis, a normal bodily process, which has been linked to potential benefits for brain function. Importantly, past research found that KME supplements do not cause serious side effects, and participants usually tolerated them well.

Although the trial under consideration is in an earlier stage, existing evidence suggests that KME supplements are unlikely to cause harm when used as directed. However, it is important to consult a doctor about any concerns or questions before joining the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cognitive impairment?

Unlike standard treatments for cognitive impairment, which often rely on medications that target neurotransmitter levels, the ketone monoester (KME) supplement offers a novel approach by providing an alternative energy source for the brain. Most treatments aim to modify chemical signaling, but KME works by supplying ketones, which can be used as fuel when glucose metabolism is impaired. Researchers are excited about this treatment because it has the potential to boost brain energy levels rapidly, possibly showing benefits in just 14 days.

What evidence suggests that ketone monoester supplementation might be an effective treatment for cognitive impairment?

This trial will compare the effects of a ketone monoester (KME) supplement with a placebo supplement. Studies have shown that KME supplements can positively affect brain function. Specifically, one study found that taking KME helped reduce the decline in thinking ability during challenging situations, such as low oxygen levels. Other research suggests that KME can slightly improve thinking skills, with a noticeable positive effect. KME safely increases ketone levels in the blood, which are believed to support brain health. Overall, early findings suggest that KME could help improve brain function in people facing cognitive challenges. ^{1 2 3 5 6}

Who Is on the Research Team?

Jeremy Walsh, PhD

Principal Investigator

McMaster University

Are You a Good Fit for This Trial?

This trial is for older adults aged 55-75 who are experiencing mild cognitive impairment or subjective cognitive decline. Participants should be interested in testing whether a ketone supplement can improve brain function and blood flow.

Inclusion Criteria

Being objectively cognitively normal as determined by a Montreal Cognitive Assessment (MoCA) score ≥26 with independent living and ambulating

SCD will be determined using the Prospective-Retrospective Memory Questionnaire (PRMQ) following the SCD Initiative Working Group framework

Exclusion Criteria

Having MRI contraindications

I have had a heart attack or stroke in the past.

History of smoking

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 visit

1 visit (in-person)

Treatment Period 1

Participants receive either KME or placebo supplementation for 14 days

14 days

2 visits (in-person)

Washout

Participants undergo a washout period before switching conditions

Duration not specified

Treatment Period 2

Participants receive the alternate condition (KME or placebo) for 14 days

14 days

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ketone monoester (KME) supplement
• Placebo supplement

Trial Overview The study tests the effects of a ketone monoester (KME) supplement versus a placebo on brain health in older adults. It measures cognition, cerebral blood flow, brain connectivity, vascular function, and blood factors after one dose and two weeks of daily use.

How Is the Trial Designed?

Group I: Ketone monoester (KME) supplement Experimental Treatment 1 Intervention

Participants will be instructed to consume a ketone monoester (KME) supplement prior to each meal (3x/day) for 14 days.

Group II: Placebo supplement Placebo Group 1 Intervention

Participants will be instructed to consume a bottle of placebo supplement prior to each meal (3x/day) for 14 days.

Who Is Running the Clinical Trial?

McMaster University

Lead Sponsor

Trials

936

Recruited

2,630,000+

Heart and Stroke Foundation of Canada

Collaborator

Trials

131

Recruited

72,600+

Published Research Related to This Trial

In a study involving 80 healthy older adults, the medium-chain triglyceride GSK2981710 increased plasma β-hydroxybutyrate (BHB) levels but did not lead to significant improvements in cognitive function or memory-related neuronal activity over 14 days.

The most common side effect was diarrhea, affecting 100% of participants in the initial part of the study, indicating that while GSK2981710 is generally well-tolerated, it may cause gastrointestinal discomfort.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of GSK2981710, a medium-chain triglyceride, on cognitive function in healthy older participants: A randomised, placebo-controlled study. O'Neill, BV., Dodds, CM., Miller, SR., et al.[2020]

In a study involving nine recreationally active men, ketone monoester (KME) supplementation was found to reduce cognitive fatigue during a simulated soccer match, leading to a smaller decrease in cognitive performance compared to a placebo.

KME also lowered blood glucose and lactate levels during exercise, suggesting it may help spare carbohydrates, which could be beneficial for athletes during high-intensity activities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketone Ester Supplementation Improves Some Aspects of Cognitive Function during a Simulated Soccer Match after Induced Mental Fatigue. Quinones, MD., Lemon, PWR.[2023]

Ingesting a ketone monoester (KME) with carbohydrates (CHO) increased blood levels of β-hydroxybutyrate and decreased glucose and lactate during exercise, indicating a shift in energy metabolism.

While the KME + CHO combination did not improve cycling performance times in a 10-km time trial, it significantly enhanced cognitive performance, leading to faster reaction times and improved task accuracy in trained females.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Ketone Monoester with Carbohydrate Improves Cognitive Measures Post-Exercise, but not Performance in Trained Females. Waldman, HS., O'Neal, EK., Barker, GA., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11442756/

Ketone monoester attenuates declines in cognitive ... Acute ingestion of KME attenuated the decline in cognitive performance during acute severe hypoxic exposure, which coincided with attenuation of ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT07051655

The Effects of Exogenous Ketones on Cognitive Function 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 ...

3. medrxiv.org medrxiv.org/content/10.1101/2025.09.17.25335999v1.full-text

The Effect of Exogenous Ketone Bodies on Cognition in ... Results indicate that EK administration has a modest but statistically significant positive effect on cognitive performance (SMD = 0.26, 95% CI: ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2274580724003613

Ketone Ester Effects on Biomarkers of Brain Metabolism ... This is the first study to investigate the AD-biomarker and cognitive effects of KME in humans. Ketone monoester is safe, tolerable, induces robust ketosis.

5. frontiersin.org frontiersin.org/journals/physiology/articles/10.3389/fphys.2024.1411421/full

Effect of ketone monoester supplementation on elite ... First, there is evidence that exogenous ketone ingestion can mitigate the decline in cognitive performance after intense exercising (Evans and ...

6. ccforum.biomedcentral.com ccforum.biomedcentral.com/articles/10.1186/s13054-025-05680-5

Potential therapeutic benefit of exogenous ketone ester ... Additionally, preliminary human studies have demonstrated cognitive benefits and patient tolerance of ketone supplementation. Although data in ...