Therapeutic Diets for Alzheimer's Disease

(TDAD Trial)

Overseen By Jessica Keller, MS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Kansas Medical Center

Disqualifiers: Insulin-requiring diabetes, Cancer, Cardiac event, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how two specific diets might impact thinking and memory in people with Alzheimer's disease. One group will follow a ketogenic diet, high in fats and low in carbohydrates, while the other will follow the Therapeutic Lifestyles Changes diet, balanced with moderate fats and low cholesterol. The researchers aim to determine if these dietary changes can improve cognitive function. This trial suits individuals diagnosed with Alzheimer's who have not changed their medication in the last month. As an unphased trial, it offers a unique opportunity to contribute to understanding dietary impacts on Alzheimer's, potentially benefiting future treatments.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must not have had any medication changes within the past 30 days to be eligible.

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 must not have had any medication changes in the past 30 days before joining.

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

Research has shown that the ketogenic diet, high in fat and low in carbohydrates, can be safe for many people. Some studies on its use in Alzheimer's patients found it generally well-tolerated. However, side effects like digestive issues or changes in energy levels may occur as the body adjusts to burning fats instead of carbs.

For the Therapeutic Lifestyles Changes Diet, research suggests it is generally safe and beneficial. This diet includes a balance of fats, proteins, and carbohydrates, with an emphasis on fruits and vegetables. It has been linked to improved heart health, which might also support brain health.

Both diets have been studied, but individual reactions can vary. Monitoring the body's response and consulting healthcare providers about any concerns is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer dietary approaches to managing Alzheimer's disease, a departure from the current standard of care that primarily involves medications like cholinesterase inhibitors and memantine. The Ketogenic Diet, with its high-fat, low-carb ratio, aims to provide the brain with alternative fuel sources, potentially improving cognitive functions. Meanwhile, the Therapeutic Lifestyles Changes Diet emphasizes a balanced approach with controlled fat and cholesterol intake, promoting overall heart health, which is crucial for brain health. These lifestyle-based interventions could offer more holistic, accessible options for individuals seeking alternatives to traditional medication.

What evidence suggests that this trial's treatments could be effective for Alzheimer's disease?

Research has shown that the ketogenic diet, one of the treatment options in this trial, might help people with Alzheimer's by providing the brain with an alternative energy source through fats and ketones instead of sugar. This can be beneficial because people with Alzheimer's often have difficulty using sugar in their brains. Some studies have found that this high-fat, low-carb diet can improve thinking and memory.

The Therapeutic Lifestyles Changes (TLC) diet, another treatment option in this trial, is lower in fat and higher in carbs. Research suggests that significant changes in diet and lifestyle, like those in the TLC diet, might slow memory loss and even boost brain function in people with Alzheimer's. Both diets take different approaches, but studies indicate they might help with memory and thinking problems related to Alzheimer's. ^{1 3 4 5 6}

Are You a Good Fit for This Trial?

This trial is for individuals aged 50 to 90 with Alzheimer's Disease, as diagnosed by McKhann et al. criteria. Participants must speak English, have a stable medication regimen for the past month, and score 0.5 or 1 on the CDR scale. They need a study partner and cannot be in nursing care or another trial, nor can they have renal stones, insulin-requiring diabetes, recent cancer treatments or cardiac events.

Inclusion Criteria

Agreed cooperation from an appropriate study partner

You have a CDR global score of 0.5 or 1.

No medication changes within the past 30 days

Exclusion Criteria

I do not have serious health issues like insulin diabetes, recent cancer treatments, or heart problems.

I have had kidney stones in the past.

You live in a nursing home or a special care unit for dementia, or you have difficulty controlling your diet.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Ketogenic Diet Treatment

Participants adhere to a 1:1 ketogenic diet with supplements for 3 months

12 weeks

Monthly visits for dietary assessment

Washout Period

Participants halt adherence to the ketogenic diet and resume their normal diet

4 weeks

Therapeutic Lifestyles Changes Diet

Participants adhere to the Therapeutic Lifestyles Changes diet

12 weeks

Monthly visits for dietary assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ketogenic Diet
• Therapeutic Lifestyles Changes Diet

Trial Overview The study aims to compare how two diets—the Ketogenic Diet and Therapeutic Lifestyles Changes Diet—affect cognitive function in Alzheimer's patients. Researchers will observe changes in cognition to determine any potential benefits of these dietary interventions.

How Is the Trial Designed?

Group I: Ketogenic Diet Experimental Treatment 1 Intervention

Study partners will be instructed to assist participants in adherence to a 1:1 ketogenic diet (approximately 70% fat, \<10% carbohydrate, and 20% protein as energy). The diet will encourage ≥4 servings of non-starchy vegetables and 1/2 cup of berries daily. Participants will be provided an emulsified medium chain triglyceride supplement with a target intake of 1-2 tablespoons per day and micronutrient supplements consisting of multivitamin, vitamin D, calcium, and phosphorus. After the 3-month ketogenic diet, participants will complete a 1-month washout period in which they halt adherence to the ketogenic diet and resume their normal diet.

Group II: Therapeutic Lifestyles Changes Diet Active Control 1 Intervention

Study partners will be instructed to assist participants in adherence to the Therapeutic Lifestyles Changes diet. The diet consists of 20-35% fat, 50-60% carbohydrate, and \~15% protein as energy. Fat intake will comprise \<7% saturated fat, ≤20% monounsaturated fat, and ≤10% polyunsaturated fat as total energy. Cholesterol consumption will be ≤200mg per day. Participants are encouraged to eat ≥2 servings of fruit and ≥5 servings of vegetables per day.

Who Is Running the Clinical Trial?

University of Kansas Medical Center

Lead Sponsor

Trials

527

Recruited

181,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Published Research Related to This Trial

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 case report of a 47-year-old woman with Down syndrome and Alzheimer's disease showed that a ketogenic diet led to significant cognitive improvement, as evidenced by an increase in her Activities of Daily Living Scale score from 34 to 58 over just 6 weeks.

This case highlights the potential of ketogenic diets not only in treating epilepsy but also in improving cognitive function in patients with neurodegenerative diseases, suggesting a broader application for neuroketotherapeutics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case report: Ketogenic diet acutely improves cognitive function in patient with Down syndrome and Alzheimer's disease. Bosworth, A., Loh, V., Stranahan, BN., et al.[2023]

The Mediterranean and Japanese-style diets, rich in nutrients like vitamin E, folate, and omega-3 fatty acids, are recommended for preventing and managing Alzheimer's disease, as they may help protect against cognitive decline.

Insulin signaling disturbances in the brains of Alzheimer's patients suggest that alternative energy sources, like medium chain triglyceride ketone bodies, could be beneficial, highlighting the importance of dietary choices that support brain health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prevention of Alzheimer's Disease and Nutrients]. Otsuka, M.[2016]

The review provides evidence that ketogenic diet therapies can be effective in managing adult epilepsy, malignant glioma, and Alzheimer's disease, suggesting a potential therapeutic role in these conditions.

It also addresses strategies for managing adverse effects and improving compliance with ketogenic diets, which is crucial for their successful implementation in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Expanding Role of Ketogenic Diets in Adult Neurological Disorders. McDonald, TJW., Cervenka, MC.[2023]

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]

A phase I/II clinical trial involving 27 patients with mild cognitive impairment or early Alzheimer's disease tested a modified Atkins diet (MAD) to induce ketone production, which may provide an alternative energy source for the brain.

Preliminary results showed that participants in the MAD group who produced trace amounts of ketones experienced a significant improvement in memory scores and reported increased energy, suggesting that even small amounts of ketones could benefit cognitive function in early Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary Report on the Feasibility and Efficacy of the Modified Atkins Diet for Treatment of Mild Cognitive Impairment and Early Alzheimer's Disease. Brandt, J., Buchholz, A., Henry-Barron, B., et al.[2020]

In a study of 200 older patients (median age 70) on a ketogenic diet, 67% reported beneficial outcomes, including significant weight loss for 79% of those seeking it, improved glucose control for 54% of those with diabetes, and positive effects on cancer outcomes for 63% of patients pursuing that goal.

While the ketogenic diet showed promise for various health issues in older adults, 15% of participants experienced adverse events, including dyslipidemia and constipation, highlighting the need for careful monitoring in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can older patients adopt and maintain a ketogenic diet? An observational study in support of clinical trials in older patients. Almodallal, Y., Cook, K., Lammert, LM., et al.[2023]

A ketogenic diet (KD) has shown promise in improving cognitive abilities and quality of life for patients with Alzheimer's disease (AD), with benefits observed across various stages of the disease from mild to severe.

Research indicates that once patients achieve ketosis, cognitive improvements are consistently noted, suggesting that further investigation into the mechanisms behind these effects could lead to new strategies for managing or preventing cognitive decline in AD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A narrative review on the effects of a ketogenic diet on patients with Alzheimer's disease. Tabaie, EA., Reddy, AJ., Brahmbhatt, H.[2022]

Clinical studies suggest that the ketogenic diet (KD) and medium-chain triglyceride (MCT) supplementation may help reduce symptoms of Alzheimer's disease (AD), although these studies are limited in size and duration.

MCT supplements can increase ketone body levels in the blood without requiring significant dietary changes, making them a potentially safer option for patients with AD who are at risk of malnutrition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The possibility of use of the ketogenic diet and medium chain triglycerides supplementation in the support therapy of Alzheimer disease. Włodarek, D.[2023]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S1279770724003932

Effects of ketogenic diet on cognitive function of patients ... One of the ten included studies chose a common ketogenic diet (with an average macronutrient ratio of 58% fat, 29% protein, 7% fiber, and 6% net carbohydrates ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8755961/

A narrative review on the effects of a ketogenic diet ... Since patients who have Alzheimer's tend to not have effective glucose transporters within the brain [3], a diet high in fat or ketones, an alternative energy ...

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

Consuming a modified Mediterranean ketogenic diet ... KD is a high-fat and low-carbohydrate diet. This transition of the body's primary metabolic fuel from glucose to fats and ketones leads to ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6021549/

Feasibility and efficacy data from a ketogenic diet ... One potential approach includes the ketogenic diet (KD). KDs increase fat and reduce carbohydrate consumption [11]. This reduces insulin ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2213453016301355

Ketogenic diets and Alzheimer's disease The ketogenic diet is very high in fat and low in carbohydrates and is believed to simulate the effects of starvation by primarily metabolizing fat as ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6720297/

Ketogenic Diet in Alzheimer's Disease - PMC - PubMed Central These recommendations include minimizing the intake of trans fat and saturated fats, dairy products and increased consumptions of vegetables, ...