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

80 Participants Needed

Trial Summary

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.

What data supports the idea that Therapeutic Diets for Alzheimer's Disease is an effective treatment?

The available research shows that therapeutic diets like the ketogenic diet can improve cognitive abilities and quality of life for Alzheimer's patients. Studies have found that once the body enters a state called ketosis, where it uses fat instead of sugar for energy, patients with mild to severe Alzheimer's experience cognitive improvements. These diets have also been linked to better brain metabolism and reduced harmful brain deposits associated with Alzheimer's. Compared to other treatments, ketogenic diets show promise in improving brain function and reducing symptoms. ^{1 2 3 4 5}

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

Research suggests that a ketogenic diet, which is high in fats and low in carbohydrates, may help improve cognitive function and quality of life in people with Alzheimer's disease. Studies have shown that when the brain uses ketone bodies (produced during ketosis) instead of glucose, there can be improvements in memory and a reduction in symptoms associated with Alzheimer's. ^{1 2 3 4 5}

What safety data exists for therapeutic diets in Alzheimer's treatment?

The safety data for therapeutic diets, particularly ketogenic diets, in Alzheimer's treatment includes evidence from various studies. Adverse effects and compliance strategies are discussed in the literature, with some studies reporting adverse events such as dyslipidemia, constipation, and fatigue. However, these diets have shown potential benefits in cognitive improvement and symptom management in Alzheimer's patients. ^{1 3 6 7 8}

Is the ketogenic diet safe for humans?

The ketogenic diet has been used safely in humans for conditions like epilepsy and Alzheimer's disease, but some people may experience side effects like high cholesterol, constipation, and fatigue. ^{1 3 6 7 8}

Is the Ketogenic Diet a promising treatment for Alzheimer's Disease?

Yes, the Ketogenic Diet is a promising treatment for Alzheimer's Disease. Research shows it can improve memory, brain function, and reduce harmful brain changes associated with the disease. ^{3 4 7 9 10}

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

The ketogenic diet is unique for Alzheimer's treatment because it provides an alternative energy source for the brain through ketone bodies, which can be beneficial when glucose metabolism is impaired, as seen in Alzheimer's. This diet has shown potential in improving cognitive function and reducing neuroinflammation, which are not typically addressed by standard treatments. ^{3 4 7 9 10}

What is the purpose of this trial?

By doing this study, researchers hope to learn how the ketogenic and Therapeutic Lifestyles Changes diets affect cognition in patients with Alzheimer's disease.

Eligibility Criteria

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.

You have been diagnosed with Alzheimer's disease using the latest criteria by McKhann et al.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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 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]

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 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]

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]

References

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

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

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

A narrative review on the effects of a ketogenic diet on patients with Alzheimer's disease. [2022]

3. England 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. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

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

6. Switzerland pubmed.ncbi.nlm.nih.gov

The Expanding Role of Ketogenic Diets in Adult Neurological Disorders. [2023]

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

Case report: Ketogenic diet acutely improves cognitive function in patient with Down syndrome and Alzheimer's disease. [2023]

8. United States 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. [2023]

9. Netherlands 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. [2020]

10. Japan pubmed.ncbi.nlm.nih.gov

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