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

17 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the treatment Ketogenic Supplement for Alzheimer's Disease?

Research suggests that a ketogenic diet, which provides an alternative energy source for the brain, may help improve memory and cognitive function in people with Alzheimer's disease. Studies have shown that such diets can improve memory performance and increase brain energy metabolism, potentially slowing cognitive decline. ^{1 2 3 4 5}

Is the ketogenic supplement safe for humans?

Research on ketogenic diets, which are similar to ketogenic supplements, shows they are generally safe for humans, with studies indicating improved brain function and metabolism in older adults, including those at risk for Alzheimer's disease. ^{1 3 4 5 6}

How does the ketogenic supplement treatment for Alzheimer's disease differ from other treatments?

The ketogenic supplement provides an alternative energy source for the brain by using ketone bodies instead of glucose, which may help reduce neuroinflammation and improve cognitive function in Alzheimer's patients. This approach is unique because it targets brain metabolism directly, unlike most current treatments that focus on symptomatic relief. ^{1 2 4 6 7}

What is the purpose of this trial?

It is projected that by 2030, one in every five Americans will be of retirement age, and this demographic shift is expected to result in more people suffering from dementia. A key feature of the brain is its need for a constant supply of glucose and oxygen to meet the high energy costs of mental activity. This study aims to develop clinically practical, noninvasive imaging methods based on combined positron emission tomography and magnetic resonance imaging to assess brain energy in order to better understand how this critical component of brain health is impacted by aging.

Research Team

Keith St Lawrence, PhD

Principal Investigator

Lawson Research Institute

Eligibility Criteria

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

Recent participation in any procedure(s) involving radioactive agents

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

Timeline

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Ketogenic diet therapy in Alzheimer's disease: an updated review. [2023]

2. Ireland pubmed.ncbi.nlm.nih.gov

Effects of a medium-chain triglyceride-based ketogenic formula on cognitive function in patients with mild-to-moderate Alzheimer's disease. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Randomized crossover trial of a modified ketogenic diet in Alzheimer's disease. [2021]

4. United States 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. [2020]

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

Feasibility and efficacy data from a ketogenic diet intervention in Alzheimer's disease. [2023]

6. 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]

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

Efficacy and Safety of Ketone Supplementation or Ketogenic Diets for Alzheimer's Disease: A Mini Review. [2022]