Ketone Supplement for Mild Cognitive Impairment

(BREAK-AD Trial)

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Université de Sherbrooke

Must not be taking: Anti-cholinergic drugs

Disqualifiers: Diabetes, Neurodegenerative disease, Cancer, others

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a ketone supplement, Exogenous Ketone Salt (EKS), can enhance brain energy use and thinking skills in individuals with mild memory problems. Participants will take the supplement twice daily for six months. The study will compare participants taking the supplement to those taking a placebo, which is a look-alike product with no active ingredient. It suits individuals who have noticed a decline in memory, believe they could benefit from support, and are comfortable reading and speaking French. As an unphased trial, this study provides a unique opportunity to explore potential cognitive benefits from ketone supplements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you have recently changed your medication or are taking anti-cholinergic drugs (medications that block a specific neurotransmitter).

Is there any evidence suggesting that the Exogenous Ketone Salt (EKS) Supplement is likely to be safe for humans?

Research has shown that exogenous ketone salts (EKS) supplements are generally safe for use. Studies suggest these supplements might enhance brain function by providing an alternative energy source. In past research, participants using EKS did not report any serious side effects. Some experienced mild issues like stomach discomfort, but these were uncommon.

Although the specific trial phase isn't mentioned, the focus on safety and effectiveness demonstrates a good understanding of how EKS works in the body. Researchers are also studying EKS supplements for potential benefits in various brain-related conditions, further supporting their safety. Overall, the available evidence suggests that EKS is safe for use. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike standard treatments for mild cognitive impairment, which often involve medications like cholinesterase inhibitors, the exogenous ketone salt (EKS) supplement offers a novel approach by providing an alternative energy source for the brain. Researchers are excited about this treatment because it leverages ketone bodies, which can help support brain function when glucose metabolism is impaired. This new mechanism of action could potentially enhance cognitive performance and slow down cognitive decline, offering a promising alternative to existing therapies.

What evidence suggests that this treatment might be an effective treatment for mild cognitive impairment?

Research shows that exogenous ketone salts (EKS) can boost brain performance. One study found a small but real improvement in thinking skills when people used these supplements. Early evidence suggests that ketones might protect the brain or enhance its function in certain conditions. Specifically, these supplements can induce ketosis, where the body uses fat for energy, potentially supporting brain health. Although the effects are modest, they suggest possible benefits for individuals with mild memory or thinking issues. Overall, early research supports the idea that EKS supplements could help improve or maintain brain function. Participants in this trial will join either an active group receiving EKS supplements or a placebo group to evaluate these potential benefits. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for individuals with mild cognitive impairment who can understand, read, and speak French, have good vision and hearing, feel their memory has declined, and score within a specific range on cognitive tests. Excluded are those with certain medical conditions like kidney failure or recent cancer, vitamin deficiencies, drastic weight loss recently, or taking conflicting medications.

Inclusion Criteria

You have good eyesight and hearing abilities.

Have a QAF score of less than 9/30

I can understand, read, and speak French.

Exclusion Criteria

I have had active cancer within the last 2 years.

I have a chronic disease that is not well-managed.

I have had kidney stones or high calcium levels in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 15 g of the exogenous ketone salt supplement twice daily for 6 months

6 months

Regular visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Open-label extension

Participants may opt into continuation of the active product for an additional 3 months

3 months

What Are the Treatments Tested in This Trial?

Interventions

• Exogenous Ketone Salt (EKS) Supplement

Trial Overview The study is testing an exogenous ketone salt supplement given twice daily over six months against a placebo to see if it improves brain energy metabolism, cognition and quality of life in people with mild cognitive impairment. Brain imaging and plasma biomarkers will also be assessed.

How Is the Trial Designed?

Group I: Active group Experimental Treatment 1 Intervention

Participants will be on the active intervention for 6 months

Group II: Open phase on active product Active Control 1 Intervention

At the end of the 6-month randomized controlled phase, participants will be unblinded and invited to continue on the active product for an additional 3 months.

Group III: Placebo Group Placebo Group 1 Intervention

Participants will be on the placebo intervention for 6 months

Exogenous Ketone Salt (EKS) Supplement is already approved in United States for the following indications:

Approved in United States as Axona for:

• Alzheimer's disease

Who Is Running the Clinical Trial?

Université de Sherbrooke

Lead Sponsor

Trials

317

Recruited

79,300+

Nestlé Health Science SA

Collaborator

Trials

1

Recruited

60+

Alzheimer's Association

Collaborator

Trials

103

Recruited

44,300+

Nestle Health Science

Industry Sponsor

Trials

12

Recruited

2,200+

Published Research Related to This Trial

Exogenous ketone supplements, such as ketone salts or esters, have shown potential benefits for metabolic health, cognitive function, and cardiovascular health, particularly in lowering blood glucose and improving cognitive performance, which may be useful for conditions like type 2 diabetes and neurological diseases.

Current research primarily involves pre-clinical models, and while some human studies support the benefits of exogenous ketones, further clinical validation is needed, especially regarding long-term effects on cardiovascular health and lipid profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exogenous ketone supplementation: an emerging tool for physiologists with potential as a metabolic therapy. Falkenhain, K., Islam, H., Little, JP.[2023]

Recent studies indicate that ketogenic diets (KD) and ketogenic supplements (KS) may reduce neuroinflammation and improve cognitive function in Alzheimer's disease (AD), with evidence from both animal models and human trials.

In humans, KD/KS showed significant cognitive benefits and improved brain metabolism, with acceptable adherence and only minor gastrointestinal side effects, suggesting potential as a therapeutic approach for AD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketogenic diet therapy in Alzheimer's disease: an updated review. Lilamand, M., Mouton-Liger, F., Paquet, C.[2023]

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 6 participants with mild cognitive impairment (MCI), supplementation with 56 g/day of medium chain triglycerides (MCTs) for 24 weeks significantly increased serum ketone bodies and improved memory performance.

The placebo group did not show any cognitive improvements, suggesting that MCT supplementation may be a promising approach for enhancing brain function in individuals with MCI, warranting further research with larger trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot feasibility and safety study examining the effect of medium chain triglyceride supplementation in subjects with mild cognitive impairment: A randomized controlled trial. Rebello, CJ., Keller, JN., Liu, AG., 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]

In a study of 52 participants with mild cognitive impairment (MCI), a daily dose of 30 g of ketogenic medium chain triglycerides (kMCT) significantly increased brain ketone metabolism by 230%, while glucose uptake remained unchanged.

The kMCT treatment led to improvements in cognitive performance, including episodic memory and processing speed, suggesting that providing ketones as an alternative fuel can enhance brain function in individuals with MCI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A ketogenic drink improves brain energy and some measures of cognition in mild cognitive impairment. Fortier, M., Castellano, CA., Croteau, E., et al.[2020]

Exogenous ketone drinks, both monoester and salt forms, can cause mild gastrointestinal symptoms, with symptom severity influenced by the dose and type of drink consumed, as well as whether the individual is at rest or exercising.

High-dose ketone salt drinks resulted in more gastrointestinal symptoms compared to low-dose versions, but overall, symptoms were acute and resolved by the end of the study, indicating that while they may cause discomfort, they are generally tolerable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastrointestinal Effects of Exogenous Ketone Drinks are Infrequent, Mild, and Vary According to Ketone Compound and Dose. Stubbs, BJ., Cox, PJ., Kirk, T., et al.[2021]

In a study involving 14 healthy young adults, both ketone monoester (KME) and ketone monoester/salt (KMES) formulations significantly increased circulating R-beta-hydroxybutyrate (R-βHB) levels in a dose-dependent manner, with KME10 reaching a peak concentration of 2.4 mM after 15 minutes.

Both formulations were well-tolerated, but KMES was slightly more acceptable due to a better taste, while KME was associated with a more frequent decrease in appetite, indicating that user experience may vary between different ketone products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability and Acceptability of an Exogenous Ketone Monoester and Ketone Monoester/Salt Formulation in Humans. Bolyard, ML., Graziano, CM., Fontaine, KR., et al.[2023]

The BENEFIC trial, a 6-month randomized controlled study, demonstrated that a ketogenic medium-chain triglyceride (kMCT) drink improved cognitive performance in individuals with mild cognitive impairment (MCI) compared to a placebo.

Ketogenic supplements provide an alternative energy source for brain cells, suggesting that nutritional interventions like kMCTs could be a promising approach to managing MCI, especially given the lack of approved pharmacologic treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mild cognitive impairment: when nutrition helps brain energy rescue-a report from the EuGMS 2020 Congress. Cunnane, SC., Sieber, CC., Swerdlow, RH., et al.[2022]

A 12-week intervention combining a ketogenic diet, high-intensity interval training, and memory training significantly improved memory function in a 57-year-old woman with mild cognitive impairment, raising her Montreal Cognitive Assessment score from 22/30 to 30/30, indicating normal cognitive function.

The intervention also led to statistically significant improvements in physiological biomarkers related to metabolic syndrome, suggesting that ketogenic nutrition may help address both cognitive decline and metabolic health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketogenic diet, high intensity interval training (HIIT) and memory training in the treatment of mild cognitive impairment: A case study. Dahlgren, K., Gibas, KJ.[2018]

Citations

1. 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: ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8734638/

Ketone Supplementation: Meeting the Needs of the Brain in ... Preliminary evidence suggests ketosis induced by exogenous ketones may attenuate damage or improve cognitive and motor performance in neurological conditions ...

3. trialx.com trialx.com/clinical-trials/listings/259126/brain-energy-activation-with-ketones-to-prevent-alzheimers-disease/

BRain Energy Activation With Ketones to Prevent ... Overview. A six month randomized controlled intervention with an exogenous ketone salt (EKS) supplement in mild cognitive impairment.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9947355/

Ketogenic interventions in mild cognitive impairment ... Supplementation with the ketogenic MCT formula was associated with significant improvements in cognitive tests compared to placebo. No significant effect of ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT07051655

The Effects of Exogenous Ketones on Cognitive Function Prior studies have demonstrated that KME improves cognition in individuals with Alzheimer's disease and mild cognitive impairment; however, its effects in ...

6. academic.oup.com academic.oup.com/nutritionreviews/article/83/3/e1034/7720512?rss=1

Efficacy and Safety of Exogenous Ketones in People with Mild ... Studies reporting cognitive function efficacy and safety outcomes from randomized controlled trials of exogenic ketones in patients with mild ...