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

(BEAT-AD Trial)

Overseen By Lauren Latham

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?

This trial aims to compare the effects of two special diets on adults with mild cognitive impairment, an early stage of memory loss. Participants will follow either a ketogenic diet, high in fats and low in carbohydrates, or a low-fat diet (also known as the American Heart Association Diet), for 16 weeks. Researchers will measure changes in cognitive abilities, blood flow to the brain, and certain proteins and hormones to determine if these diets can improve memory and brain function. This trial is for individuals with mild memory problems who can maintain stable health and are willing to adhere to a specific diet during the study period. As an unphased trial, it offers participants the chance to contribute to groundbreaking research on dietary impacts on cognitive health.

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

Research has shown that the ketogenic (low-carb) diet and the low-fat diet in this study yield different safety outcomes.

The ketogenic diet might aid in managing Alzheimer's, but ongoing research seeks to determine the best diet for brain health. Most individuals tolerate this diet well, though some may experience fatigue or stomach issues.

The low-fat diet is recognized for promoting heart health and is safe for most people. However, some studies suggest that excessively lowering cholesterol might not benefit brain health.

Both diets are generally safe, but individual experiences can vary. Always consult a doctor before making significant dietary changes. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these dietary approaches for Alzheimer's disease because they explore how altering energy sources might impact brain health. The Modified Mediterranean Ketogenic Diet is unique in that it induces ketosis by significantly reducing carbohydrate intake to under 20 grams per day, potentially offering a new way to fuel the brain that differs from the typical reliance on glucose. On the other hand, the American Heart Association Diet emphasizes a low-fat, high-carbohydrate approach that focuses on fiber-rich foods. These diets are distinctive because they may offer alternative pathways to manage or possibly slow down Alzheimer's progression, contrasting with standard treatments that predominantly target symptoms rather than underlying dietary contributions to brain function.

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

This trial will compare the Modified Mediterranean Ketogenic Diet (MMKD) with the American Heart Association Diet (AHAD) to assess their effects on Alzheimer's disease. Studies have shown that the MMKD might slow down or even prevent Alzheimer's disease. Research suggests that this diet alters certain proteins and hormones related to brain health and improves markers linked to Alzheimer's. Additionally, the MMKD may enhance gut health, which is connected to brain function. In contrast, the AHAD emphasizes low-fat, high-carbohydrate foods to support overall health, but there is less direct evidence of its benefits for Alzheimer's disease. Overall, the MMKD appears more promising for directly addressing Alzheimer's risk factors. ^{3 6 7 8 9}

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

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

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

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 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]

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]

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]

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]

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]

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]

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]

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 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]

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]

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]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11711287/

Consuming a modified Mediterranean ketogenic diet reverses ...

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

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT2984540

Effect of a Modified Ketogenic-Mediterranean Diet on ...

The data collected will help determine changes in cognitive function, brain structure and function, and levels of certain proteins and hormones in body fluids.

3.

sciencedirect.com

sciencedirect.com/science/article/pii/S2352396419305547

Modified Mediterranean-ketogenic diet modulates gut ...

A modified Mediterranean-ketogenic diet (MMKD) alters the gut microbiome signature in association with cerebrospinal fluid (CSF) AD biomarkers.

4.

newsroom.wakehealth.edu

newsroom.wakehealth.edu/news-releases/2023/04/modified-mediterranean-ketogenic-diet-may-benefit-adults-at-risk-for-alzheimers-disease

Modified Mediterranean Ketogenic Diet May Benefit Adults at ...

Following a Mediterranean-based ketogenic diet may decrease the risk of Alzheimer's disease, according to a new study from scientists at Wake Forest University ...

5.

nature.com

nature.com/articles/s44324-024-00016-3

Serum and CSF metabolomics analysis shows ...

Our findings highlight that MMKD can improve AD-related risk factors, reverse some metabolic disturbances associated with AD, and align metabolic changes ...

6.

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.

7.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39779882/

Consuming a modified Mediterranean ketogenic diet reverses ...

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

8.

sciencedirect.com

sciencedirect.com/science/article/pii/S1279770723008539

The Ketogenic Diet and Alzheimer's Disease

Research suggests that diet may play a role in AD, but it is inconclusive relative to which dietary approach provides the most neuroprotective effects.

9.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7231139/

Influence of the Mediterranean and Ketogenic Diets on ...

The aim of the present narrative review is to overview the existing research on the efficacy of MedDi and KD against AD-related cognitive decline.