Ketogenic Diet vs Low-Fat Diet for Alzheimer's Disease

(BEAT-AD Trial)

Overseen By Amy Hughes, AAS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Wake Forest University Health Sciences

Must not be taking: Diabetes medications

Disqualifiers: Neurodegenerative illness, Stroke, Psychiatric disorders, Diabetes, others

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

Compensation: Varies

Number of Visits: 24

Duration: 16 weeks

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The Brain Energy for Amyloid Transformation in AD (Alzheimer's disease) or BEAT-AD study will compare the effects of a ketogenic low-carbohydrate diet and a low-fat diet in adults with mild cognitive impairment. The data collected will help determine whether diet interventions induce changes in cognitive function, cerebral blood flow, and levels of certain proteins and hormones in body fluids. The study will include volunteers who have mild cognitive impairment, who will be randomly assigned to receive either a ketogenic low-carbohydrate diet or a low-fat diet for 16-weeks, with follow-up assessment 8 weeks after diet completion. Study measures, clinic visits and phone sessions will occur at baseline and throughout the 24-week study. Participant will follow either a low-carbohydrate or low-fat diet that will be individually planned with help from a study dietitian. After completing the study diet for 16 weeks, participants will resume their normal diet. The final visits will occur at week 24 (8 weeks after the completing the diet). At the end of the 24-week study, participants will be given the opportunity to meet with the study dietitian for education and assistance with planning a healthy diet.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it requires that you have been stable on your medications for at least 4 weeks before starting the study. It's best to discuss your specific medications with the study physician.

Is the ketogenic diet safe for humans?

The ketogenic diet is generally considered safe for humans, but some people may experience side effects like changes in cholesterol levels, constipation, and fatigue. Long-term use could potentially affect kidney function, especially in those with existing kidney issues. ^{1 2 3 4 5}

How is the ketogenic diet treatment different from other treatments for Alzheimer's disease?

The ketogenic diet is unique because it provides an alternative fuel for the brain, using ketone bodies instead of glucose, which may help reduce neuroinflammation and improve brain metabolism in Alzheimer's patients. Unlike other treatments, it focuses on dietary changes to potentially slow cognitive decline and improve Alzheimer's biomarkers. ^{6 7 8 9 10}

What data supports the effectiveness of the ketogenic diet treatment for Alzheimer's disease?

Research suggests that a modified ketogenic diet may improve brain function in older adults at risk for Alzheimer's by providing an alternative energy source for the brain, improving certain biomarkers, and enhancing memory performance. Additionally, fish and omega-3 fatty acids, which are components of some ketogenic diets, have been linked to slower cognitive decline in older adults. ^{6 7 10 11 12}

Who Is on the Research Team?

Suzanne Craft

Principal Investigator

Wake Forest University Health Sciences

Are You a Good Fit for This Trial?

Adults with mild cognitive impairment who are stable medically and on medications can join this study. They need an informant to provide additional information about them. People with significant sensory impairments, liver issues, other neurodegenerative diseases besides MCI, MRI contraindications, active cancer (except certain types), recent seizures or strokes, major psychiatric disorders, diabetes needing medication, or serious illnesses cannot participate.

Inclusion Criteria

I have been diagnosed with mild memory loss.

My medications have been the same for at least 4 weeks.

Able to complete baseline assessments

Exclusion Criteria

I haven't had a serious brain injury, lost consciousness, or been diagnosed with a major psychiatric disorder in the past year.

Sensory impairment (i.e.: visual or auditory) that would preclude the participant from participating in the protocol

I have been diagnosed with a neurodegenerative illness other than MCI.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants follow either a ketogenic low-carbohydrate diet or a low-fat diet for 16 weeks, with personalized nutritional guidance and compliance assessment by a dietitian.

16 weeks

Regular clinic visits and phone sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment, with final assessments occurring 8 weeks after diet completion.

8 weeks

Final visits at week 24

Diet Education

Participants have the opportunity to meet with the study dietitian for education and assistance with planning a healthy diet after the study.

What Are the Treatments Tested in This Trial?

Interventions

• Low-carbohydrate/High-fat Diet
• Low-fat/High-carbohydrate Diet

Trial Overview The BEAT-AD study is testing if a ketogenic low-carbohydrate diet versus a low-fat diet affects cognitive function in adults with mild cognitive impairment over 16 weeks. Participants will be randomly assigned to one of the diets and monitored for changes in brain function and biomarkers related to Alzheimer's disease.

How Is the Trial Designed?

Group I: Modified Mediterranean Ketogenic Diet Experimental Treatment 1 Intervention

The MMKD is a low carbohydrate/high fat diet aimed at inducing ketosis, as the experimental diet in the proposed study. Participants on the MMKD will keep their daily carbohydrate consumption below 20 grams per day throughout the 4 month intervention.The MMKD group will be supplied with extra virgin olive oil during their in person visits to use as a source of fat in their diet, and will be encouraged to eat plentiful fish, lean meats, and nutrient rich foods that meet the requirement of \<20 grams total carbohydrates per day. Participants will receive a daily multivitamin (Centrum Silver) over the course of the study and instructed to take 1 tablet each day while on the diet.

Group II: American Heart Association Diet Experimental Treatment 1 Intervention

The American Heart Association Diet (AHAD), is a low fat/high carbohydrate diet (\<40 grams/day) will be used as the control diet. Participants on the AHAD will be encouraged to limit their amount of fat intake to \<40 grams/day, while eating plentiful fruits, vegetables, and carbohydrates containing adequate fiber. Participants will receive the same daily multivitamin supplement (Centrum Silver) over the course of the study and instructed to take 1 tablet each day while on the diet.

Who Is Running the Clinical Trial?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Published Research Related to This Trial

In a study of 75 Alzheimer's patients over 3 months, the type of diet (normal, diabetic, or texture-modified) significantly influenced weight loss, with texture-modified diets being the most common among participants.

Non-malnourished patients showed notable differences in weight loss rates based on their diet type, highlighting the importance of tailored dietary approaches for managing weight in Alzheimer's patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Impact of Diet Type on Weight Loss in Patients with Alzheimer's Disease. Nakamura, T.[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]

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 prospective cohort study found that higher seafood consumption is linked to fewer brain plaques and tangles in elderly individuals, suggesting a potential protective effect against cognitive decline.

While some evidence supports the cognitive benefits of n-3 fatty acids in healthy older adults and those with mild cognitive impairment, a Cochrane review concluded that n-3 fatty acids do not provide significant benefits for patients with mild to moderate Alzheimer's disease over six months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fish consumption and omega-3 fatty acid supplementation for prevention or treatment of cognitive decline, dementia or Alzheimer's disease in older adults - any news? Cederholm, T.[2018]

In a study of 569 older adults, a higher adherence to the MIND diet was linked to better cognitive functioning close to death, indicating its potential protective effects against cognitive decline.

Importantly, this positive association between the MIND diet and cognition remained significant even after accounting for common brain pathologies like Alzheimer's disease, suggesting that the diet may enhance cognitive resilience independently of these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MIND Diet, Common Brain Pathologies, and Cognition in Community-Dwelling Older Adults. Dhana, K., James, BD., Agarwal, P., et al.[2021]

Low-carbohydrate/high-protein diets were found to be more effective than low-fat/high-carbohydrate diets for weight loss and improving cardiovascular risk factors, based on a systematic review of 13 randomized controlled trials lasting at least 6 months.

Participants showed a preference for low-carbohydrate diets, as indicated by a higher dropout rate in the low-fat diet group, suggesting that these diets may be more sustainable for long-term weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review of randomized controlled trials of low-carbohydrate vs. low-fat/low-calorie diets in the management of obesity and its comorbidities. Hession, M., Rolland, C., Kulkarni, U., et al.[2022]

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]

Ketogenic diets, which are low in carbohydrates and high in fats, have been shown to be effective for weight loss and can improve triglyceride and HDL cholesterol levels compared to low-fat diets.

Despite concerns about their high fat content, the degree of carbohydrate restriction needed to achieve ketosis is still unclear, indicating a need for more standardized research on these diets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketogenic diets for weight loss: A review of their principles, safety and efficacy. Sumithran, P., Proietto, J.[2022]

In a clinical trial with 137 participants, both low-carbohydrate and moderate-carbohydrate diets led to significant weight loss and reductions in body measurements compared to a control group, with the low-carbohydrate diet resulting in a greater percentage of body fat loss.

The low-carbohydrate diet also showed superior improvements in various cholesterol levels (including LDL and HDL) compared to the moderate-carbohydrate diet, suggesting it may be more effective for cardiovascular risk reduction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Moderate-carbohydrate low-fat versus low-carbohydrate high-fat meal replacements for weight loss. Wal, JS., McBurney, MI., Moellering, N., et al.[2013]

The Mediterranean diet, characterized by its balanced intake of macronutrients and micronutrients, is recommended for long-term weight maintenance and health benefits, unlike short-term restrictive diets that are difficult to sustain.

Low-carbohydrate ketogenic diets may pose medical risks, particularly for individuals with obesity, as they can lead to metabolic acidosis and renal issues, potentially reducing life expectancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-carbohydrate ketogenic diets in body weight control: A recurrent plaguing issue of fad diets? Schutz, Y., Montani, JP., Dulloo, AG.[2021]

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]

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

The Impact of Diet Type on Weight Loss in Patients with Alzheimer's Disease. [2021]

2. 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]

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

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

4. England pubmed.ncbi.nlm.nih.gov

Fish consumption and omega-3 fatty acid supplementation for prevention or treatment of cognitive decline, dementia or Alzheimer's disease in older adults - any news? [2018]

5. Netherlands pubmed.ncbi.nlm.nih.gov

MIND Diet, Common Brain Pathologies, and Cognition in Community-Dwelling Older Adults. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Systematic review of randomized controlled trials of low-carbohydrate vs. low-fat/low-calorie diets in the management of obesity and its comorbidities. [2022]

7. 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]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Ketogenic diets for weight loss: A review of their principles, safety and efficacy. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Moderate-carbohydrate low-fat versus low-carbohydrate high-fat meal replacements for weight loss. [2013]

10. England pubmed.ncbi.nlm.nih.gov

Low-carbohydrate ketogenic diets in body weight control: A recurrent plaguing issue of fad diets? [2021]

11. Switzerland pubmed.ncbi.nlm.nih.gov

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

12. 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]