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

48 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this randomized placebo controlled crossover trial is investigate the effects of short-term ketone monoester (KME) supplementation to brain function in older adults with subjective cognitive decline. We will test the hypothesis that KME supplementation will increase cerebral blood flow and improve resting-state functional connectivity in the brain compared to placebo supplementation in older adults with subjective cognitive decline. Participants will be randomly assigned to either placebo of KME supplementation for 14 days. Following a washout period, participants will complete the alternate condition for 14 days. Outcome measures will be assessed before and after each intervention period.

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.

What evidence supports the effectiveness of the ketone monoester (KME) supplement treatment for cognitive impairment?

Research shows that ketone-based treatments can improve cognitive function in people with mild cognitive impairment and Alzheimer's disease by providing an alternative energy source for the brain. Studies have found that these treatments can enhance memory and general cognition, and animal studies suggest they may reduce harmful brain changes associated with Alzheimer's. ^{1 2 3 4 5}

Is ketone monoester (KME) supplementation safe for humans?

Research indicates that ketone monoester (KME) supplements are generally safe for humans, as they have been shown to safely induce ketosis (a state where the body uses fat for energy instead of carbohydrates) in studies involving both healthy adults and those with mild cognitive impairment. ^{1 5 6 7 8}

How is the ketone monoester supplement treatment different from other treatments for cognitive impairment?

The ketone monoester supplement is unique because it provides an alternative energy source for the brain by inducing ketosis, which may help improve cognitive function in conditions where the brain struggles to use glucose effectively, such as Alzheimer's disease. This approach is different from traditional treatments that do not target brain energy metabolism directly. ^{1 5 6 7 9}

Research Team

Jeremy Walsh, PhD

Principal Investigator

McMaster University

Eligibility Criteria

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

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

Having MRI contraindications

History of smoking

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

A ketogenic drink improves cognition in mild cognitive impairment: Results of a 6-month RCT. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

To Keto or Not to Keto? A Systematic Review of Randomized Controlled Trials Assessing the Effects of Ketogenic Therapy on Alzheimer Disease. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

The Efficacy of Ketogenic Therapies in the Clinical Management of People with Neurodegenerative Disease: A Systematic Review. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

A ketone ester diet exhibits anxiolytic and cognition-sparing properties, and lessens amyloid and tau pathologies in a mouse model of Alzheimer's disease. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Ketone Ester Effects on Biomarkers of Brain Metabolism and Cognitive Performance in Cognitively Intact Adults ≥ 55 Years Old. A Study Protocol for a Double-Blinded Randomized Controlled Clinical Trial. [2023]

6. England 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. [2020]

7. Switzerland pubmed.ncbi.nlm.nih.gov

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

8. Switzerland pubmed.ncbi.nlm.nih.gov

Dietary Neuroketotherapeutics for Alzheimer's Disease: An Evidence Update and the Potential Role for Diet Quality. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

A Ketone Monoester with Carbohydrate Improves Cognitive Measures Post-Exercise, but not Performance in Trained Females. [2023]