Ketogenic Supplement for Alzheimer's Disease

Overseen By Erin Pagana, NP

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Pennsylvania

Disqualifiers: Neurological disease, Mental illness, Cardio- or neurovascular disease, others

Compensation: Varies

Number of Visits: 3

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a ketogenic supplement might affect brain energy in people with Alzheimer's disease. Researchers aim to determine if this supplement can improve the brain's energy use by employing imaging that combines PET and MRI scans. Individuals with mild cognitive impairment or mild-to-moderate dementia, who have specific brain markers for Alzheimer's, may be suitable for this study. Participants will receive either the ketogenic supplement or a placebo and undergo brain imaging to compare results. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research that could lead to new insights into Alzheimer's treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that ketogenic supplements are generally safe and might improve brain function in people with Alzheimer's disease. One study found that a type of ketogenic drink improved thinking skills in individuals with mild memory problems by increasing blood ketone levels. Other studies suggest that ketogenic diets and supplements could support brain energy use affected by Alzheimer's disease.

While these findings are encouraging, some reports mention possible side effects, such as changes in blood fat levels. However, these side effects are usually mild. Overall, existing research indicates that ketogenic supplements are safe, particularly for brain health. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike standard Alzheimer's treatments like cholinesterase inhibitors or memantine, which focus on neurotransmitter activity, the ketogenic supplement offers a novel approach by potentially altering brain metabolism. Researchers are excited because this supplement may provide an alternative energy source for the brain, possibly improving cognitive function by increasing ketone levels. This metabolic shift could address the brain's reduced glucose metabolism seen in Alzheimer's, offering a fresh angle for tackling the disease's symptoms.

What evidence suggests that this ketogenic supplement might be an effective treatment for Alzheimer's?

Research has shown that ketogenic supplements may benefit people with Alzheimer's disease. A ketogenic diet prompts the body to produce ketones, which the brain can use more efficiently than glucose, particularly in individuals with mild cognitive impairment (MCI) and Alzheimer's. In this trial, participants will receive either a ketogenic supplement or a placebo. One study found that a supplement called ketogenic medium-chain triglyceride (MCT) significantly improved cognitive test scores compared to a placebo. Another study found that a ketogenic drink enhanced thinking skills in people with MCI by raising blood ketone levels. These findings suggest that ketogenic supplements might help slow or even prevent the progression of Alzheimer's disease. ^{1 2 3 5 6}

Who Is on the Research Team?

Keith St Lawrence, PhD

Principal Investigator

Lawson Research Institute

Are You a Good Fit for This Trial?

This trial is for caregivers of individuals with Alzheimer's Disease. Participants should be interested in how a ketogenic supplement might aid cognition compared to a placebo drink.

Inclusion Criteria

I have Alzheimer's with confirmed amyloid and tau, mild-to-moderate symptoms, and my BMI is between 18.5-30.

I am between 21 and 80 years old with a BMI of 18.5-30.

Exclusion Criteria

Mental illness

Contraindications to MRI (claustrophobia, metal implants, pacemakers, etc.)

Recent participation in any procedure(s) involving radioactive agents

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo two PET/MR sessions with either a ketogenic supplement or placebo to assess brain glucose and oxygen metabolism

2 weeks

2 visits (in-person)

Follow-up

Participants are monitored for cognitive function using ADAS-cog at baseline and after the second imaging session

1 week

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Ketogenic Supplement

Trial Overview

The study tests whether a ketogenic supplement can improve brain energy and cognitive function in comparison to a placebo. It uses advanced imaging methods to measure the brain's energy levels.

How Is the Trial Designed?

Group I: Alzheimer's Disease Patients - Treatment Active Control 1 Intervention

Patients within the Alzheimer's continuum will be selected based on the National Institute of Aging - Alzheimer's Association Diagnostic Framework and be either classified as having mild cognitive impairment or mild-to-moderate dementia. Participants will undergo two PET/MR sessions in which CMRGlu and CMRO2 will be imaged simultaneously by PET and qBOLD MRI. For validation, CMRO2 will also be imaged by PMROx prior to FDG injection. The study will follow a crossover design in which participants will receive ketogenic supplement prior to imaging.

Group II: Alzheimer's Disease Patients - Placebo Placebo Group 1 Intervention

Patients within the Alzheimer's continuum will be selected based on the National Institute of Aging - Alzheimer's Association Diagnostic Framework and be either classified as having mild cognitive impairment or mild-to-moderate dementia. Participants will undergo two PET/MR sessions in which CMRGlu and CMRO2 will be imaged simultaneously by PET and qBOLD MRI. For validation, CMRO2 will also be imaged by PMROx prior to FDG injection. The study will follow a crossover design in which participants will receive a placebo drink prior to imaging.

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

University of Western Ontario, Canada

Collaborator

Trials

168

Recruited

320,000+

Published Research Related to This Trial

A modified Mediterranean-ketogenic diet (MMKD) showed promising effects in older adults at risk for Alzheimer's, leading to increased cerebrospinal fluid Aβ42 levels and decreased tau, which are biomarkers associated with Alzheimer's disease.

Participants on the MMKD also experienced improved metabolic indices and increased cerebral perfusion, suggesting that this diet may help in preventing cognitive decline in at-risk individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modified ketogenic diet is associated with improved cerebrospinal fluid biomarker profile, cerebral perfusion, and cerebral ketone body uptake in older adults at risk for Alzheimer's disease: a pilot study. Neth, BJ., Mintz, A., Whitlow, C., et al.[2020]

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]

Ketogenic diets (KD) and ketogenic supplementation (KS) have shown promise in reducing neuroinflammation and β-amyloid accumulation in Alzheimer's disease (AD) models, suggesting potential therapeutic benefits.

Clinical studies indicate that KS and KD may improve cognitive function and brain metabolism in AD patients, although there are ongoing discussions about their safety and potential adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Ketone Supplementation or Ketogenic Diets for Alzheimer's Disease: A Mini Review. Lilamand, M., Mouton-Liger, F., Di Valentin, E., et al.[2022]

In a randomized crossover trial involving 26 Alzheimer's disease patients, a 12-week modified ketogenic diet led to significant improvements in daily functioning and quality of life compared to a usual diet, with patients showing increased scores on the ADCS-ADL and QOL-AD assessments.

The ketogenic diet was well-tolerated, with high adherence (81% completion) and only mild adverse effects reported, indicating it is a safe dietary intervention for individuals with Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized crossover trial of a modified ketogenic diet in Alzheimer's disease. Phillips, MCL., Deprez, LM., Mortimer, GMN., et al.[2021]

A 3-month ketogenic diet (KD) trial with 15 participants with varying stages of Alzheimer's disease showed that the diet was feasible and led to significant cognitive improvement, with an average score increase of 4.1 points on the Alzheimer's Disease Assessment Scale during the diet.

Most participants achieved ketosis, but the cognitive benefits reverted to baseline after a 1-month washout, indicating that while the KD may have short-term benefits, further research is needed to explore its long-term efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility and efficacy data from a ketogenic diet intervention in Alzheimer's disease. Taylor, MK., Sullivan, DK., Mahnken, JD., et al.[2023]

Citations

1.

sciencedirect.com

sciencedirect.com/science/article/pii/S1279770724003932

Effects of ketogenic diet on cognitive function of patients ...

Many relevant studies have shown that ketones are more easily absorbed by the brain than glucose in patients with mild cognitive impairment (MCI) and AD [5,6].

2.

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 ...

3.

alz-journals.onlinelibrary.wiley.com

alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.12206

A ketogenic drink improves cognition in mild cognitive ...

This kMCT drink improved cognitive outcomes in MCI, at least in part by increasing blood ketone level. These data support further assessment of MCI progression ...

4.

nature.com

nature.com/articles/s43856-024-00682-w

Consuming a modified Mediterranean ketogenic diet ...

These data suggest adopting this diet could potentially be a promising approach to slow down or prevent the development of Alzheimer's disease.

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8803132/

Efficacy and Safety of Ketone Supplementation or Ketogenic ...

A growing body of evidence has suggested that KD could enhance cognitive performance and hopefully postpone cognitive decline in AD. Large ...

6.

frontiersin.org

frontiersin.org/journals/nutrition/articles/10.3389/fnut.2021.807970/full

Efficacy and Safety of Ketone Supplementation or ...

In this context, KS or KD represent promising nutritional strategies to postpone cognitive decline due to AD, or even to rescue brain energy. As ...