High-Fat Diet for Alzheimer's Disease

Overseen By Angela J Hanson, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Washington

Must not be taking: Diabetes meds, Hypertension meds, Statins, Dementia meds

Disqualifiers: Diabetes, Hypertension, Dementia, Psychiatric disorders, others

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

Compensation: Varies

Number of Visits: 2

90 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires participants to stop taking certain medications. If you have hypertension, you must stop your medication for 2 weeks before the MRI visit, if safe. For significant lipid abnormalities, you need to stop medications like statins 4 weeks before the screening visit, unless they are for preventing heart attack or stroke.

What data supports the effectiveness of the treatment Heavy Cream for Alzheimer's Disease?

Research suggests that a high intake of certain fatty acids, like those found in heavy cream, may be linked to a lower risk of Alzheimer's disease. ^{1 2 3 4 5}

Is a high-fat diet safe for humans?

Some studies suggest that high intake of saturated and trans fats may increase the risk of Alzheimer's disease and other cognitive disorders, but the evidence is mixed and not all studies agree. There is no specific safety data on high-fat diets for Alzheimer's, but caution is advised due to potential links with cognitive decline. ^{1 6 7 8 9}

How does the high-fat diet treatment using heavy cream differ from other treatments for Alzheimer's disease?

The high-fat diet treatment using heavy cream is unique because it focuses on dietary changes rather than supplements or medications, and it may have different effects on memory, especially in individuals with a specific genetic risk factor (APOE ε4). This approach contrasts with omega-3 fatty acid treatments, which are derived from fish oil and target different aspects of Alzheimer's disease. ^{10 11 12 13 14}

What is the purpose of this trial?

High fat feeding (HFF) increases the risk of Alzheimer's disease (AD) but individuals who carry the AD risk gene E4 paradoxically improve after acute HFF. The investigators propose to further study this phenomenon with a clinical study to assess cerebral blood flow which can be measured by a technique called arterial spin labeling (ASL) on an MRI and is tightly related to brain metabolism.

Research Team

Angela Hanson, MD

Principal Investigator

University of Washington

Eligibility Criteria

This trial is for individuals aged 55 or older, both with and without the Alzheimer's risk gene E4. Participants must be post-menopausal women or men, able to consent, undergo an MRI, and ingest dairy. Exclusions include those on diabetes/hypertension medication (unless they can stop safely), with psychiatric disorders affecting study outcomes, metal implants incompatible with MRI, significant lipid abnormalities requiring medication (unless willing to stop), diagnosed dementia or severe cognitive impairment.

Inclusion Criteria

I am a woman who is post-menopausal for at least 1 year or have had a hysterectomy.

Able to read and understand English

My genetic test shows whether I have the APOE E4 gene.

Exclusion Criteria

I don't have severe lipid problems and can stop certain medications before the trial.

I have diabetes that needs medication, but diet control or past gestational diabetes is okay.

I can safely stop my hypertension medication for 2 weeks before the MRI.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Study Visit

Participants undergo MRI and oral triglyceride tolerance test (OTTT) after fasting

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the study visit

4 weeks

Treatment Details

Interventions

• Heavy Cream

Trial Overview The study investigates how a high-fat diet using heavy cream affects brain blood flow in people at risk of Alzheimer's disease. It focuses on differences between carriers and non-carriers of the APOE E4 gene by measuring cerebral blood flow through arterial spin labeling during an MRI scan.

Participant Groups

Group I: Intervention Experimental Treatment 1 Intervention

All participants undergo the same intervention: Drinking heavy cream and undergoing MRI.

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Findings from Research

In a study of 2612 elderly participants over an average follow-up of 4.5 years, higher dietary intakes of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were linked to a significantly lower risk of developing Alzheimer's disease (AD).

Specifically, for each increase in DHA and EPA intake, the risk of AD decreased, with hazard ratios of 0.73 and 0.74 respectively, indicating that these long-chain polyunsaturated fatty acids may offer protective benefits against AD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary fatty acids and risk of Alzheimer's disease and related dementias: Observations from the Washington Heights-Hamilton Heights-Inwood Columbia Aging Project (WHICAP). Gustafson, DR., Bäckman, K., Scarmeas, N., 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]

In a study of 231 patients with cognitive dysfunction, a body mass index (BMI) of less than 23 was found in over half of the subjects and was associated with a threefold increased risk of mortality over seven years, regardless of age, gender, or type of dementia.

During a median hospital stay of three weeks, patients experienced an average weight gain and improvement in cognitive scores, but these changes were not correlated, suggesting that while nutritional interventions may have short-term benefits, they do not necessarily translate to long-term survival improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nutritional and cognitive relationships and long-term mortality in patients with various dementia disorders. Faxén-Irving, G., Basun, H., Cederholm, T.[2006]

In a randomized trial involving 204 patients with mild to moderate Alzheimer's disease, supplementation with Omega-3 fatty acids (DHA and EPA) for 6 months led to significant weight gain and improved appetite compared to a placebo group.

Patients who did not carry the APOEepsilon4 allele and had higher plasma DHA levels were more likely to experience weight gain, suggesting that genetic factors and DHA concentration may influence the effectiveness of Omega-3 supplementation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omega-3 fatty acid supplementation effects on weight and appetite in patients with Alzheimer's disease: the omega-3 Alzheimer's disease study. Irving, GF., Freund-Levi, Y., Eriksdotter-Jönhagen, M., et al.[2015]

In a study involving 53 Alzheimer's disease patients, a whole formula diet based on lyophilised foods led to a significant increase in body weight (2.06 kg) and improvements in nutritional markers like albumin and hemoglobin compared to a control group receiving nutritional advice.

While cognitive improvements measured by the Mini Nutritional Assessment and Pfeiffer tests were not significantly different between the two groups, the whole formula diet was well-tolerated and safe, with similar rates of serious adverse events in both groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of oral administration of a whole formula diet on nutritional and cognitive status in patients with Alzheimer's disease. Salas-Salvadó, J., Torres, M., Planas, M., et al.[2006]

Higher intake of saturated fats is linked to an increased risk of Alzheimer's disease (AD) and cognitive decline, as shown in 3 out of 4 studies focused on AD and 2 out of 4 studies on cognitive decline.

The relationship between trans fat intake and dementia is less clear, with mixed results across the studies, indicating that more research is needed to understand its impact on cognitive disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Saturated and trans fats and dementia: a systematic review. Barnard, ND., Bunner, AE., Agarwal, U.[2018]

A high saturated fat and low carbohydrate ketogenic diet significantly reduced brain amyloid-beta (Abeta) levels by about 25% in a transgenic mouse model of Alzheimer's disease, suggesting a potential dietary strategy for lowering Abeta accumulation.

Despite the reduction in Abeta levels and increased ketone body production, the ketogenic diet did not lead to improvements in behavioral measures, indicating that while the diet may affect biochemical markers, it does not necessarily translate to behavioral benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A ketogenic diet reduces amyloid beta 40 and 42 in a mouse model of Alzheimer's disease. Van der Auwera, I., Wera, S., Van Leuven, F., et al.[2020]

In a study involving 3,741 participants aged around 73 years, oral supplementation with long-chain polyunsaturated fatty acids (LCPUFAs) and lutein/zeaxanthin did not show any significant improvement in cognitive function compared to a placebo over a 5-year period.

The results indicate that these specific dietary supplements do not have a measurable effect on cognitive decline in older adults at risk for age-related macular degeneration, suggesting that other dietary factors may need to be explored for cognitive health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Omega-3 Fatty Acids, Lutein/Zeaxanthin, or Other Nutrient Supplementation on Cognitive Function: The AREDS2 Randomized Clinical Trial. Chew, EY., Clemons, TE., Agrón, E., et al.[2021]

High intake of saturated and trans fatty acids is associated with an increased risk of developing dementia, while higher consumption of polyunsaturated and monounsaturated fatty acids may reduce this risk.

The review highlights the importance of dietary fat composition in maintaining blood-brain barrier function and cholesterol levels, both of which are crucial in the context of Alzheimer's disease, particularly for individuals with the apolipoprotein E-ε4 genetic risk factor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary fat composition and dementia risk. Morris, MC., Tangney, CC.[2021]

In a study using 5XFAD mice, a model for Alzheimer's disease, a high-fat diet significantly increased β-amyloid deposition and impaired cognitive function, highlighting its detrimental effects on AD pathology.

The high-fat diet also elevated oxidative stress in the brains of 5XFAD mice, suggesting that dietary fat can exacerbate Alzheimer's disease progression independently of metabolic disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Fat-Diet Intake Enhances Cerebral Amyloid Angiopathy and Cognitive Impairment in a Mouse Model of Alzheimer's Disease, Independently of Metabolic Disorders. Lin, B., Hasegawa, Y., Takane, K., et al.[2022]

In a study involving 204 patients with mild to moderate Alzheimer's disease, omega-3 fatty acid supplementation did not significantly slow cognitive decline for the overall group over 6 months, as measured by standard cognitive tests.

However, a subgroup of 32 patients with very mild cognitive dysfunction showed a significant reduction in the rate of cognitive decline, suggesting potential benefits of omega-3s for early-stage Alzheimer's patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD study: a randomized double-blind trial. Freund-Levi, Y., Eriksdotter-Jönhagen, M., Cederholm, T., et al.[2022]

In a randomized clinical trial involving 204 Alzheimer's disease patients, omega-3 supplementation did not show significant overall effects on neuropsychiatric symptoms or daily functioning, but did improve agitation in APOE4 carriers and depressive symptoms in non-APOE4 carriers.

The study highlights that while omega-3 fatty acids may not universally benefit all Alzheimer's patients, they could provide targeted improvements in specific symptoms based on genetic factors, suggesting a need for personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omega-3 supplementation in mild to moderate Alzheimer's disease: effects on neuropsychiatric symptoms. Freund-Levi, Y., Basun, H., Cederholm, T., et al.[2018]

In a study of 21 older adults, a triglyceride (TG) infusion significantly increased total lipid levels in cerebrospinal fluid (CSF), indicating that dietary lipids can influence CNS lipid profiles.

The lipid changes observed were affected by the presence of the APOE ε4 gene, suggesting that genetic factors may play a role in how the central nervous system processes lipids, which could be relevant to Alzheimer's disease risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerebrospinal fluid lipidomics: effects of an intravenous triglyceride infusion and apoE status. Hanson, AJ., Banks, WA., Bettcher, LF., et al.[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]

References

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

Dietary fatty acids and risk of Alzheimer's disease and related dementias: Observations from the Washington Heights-Hamilton Heights-Inwood Columbia Aging Project (WHICAP). [2021]

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

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

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

Nutritional and cognitive relationships and long-term mortality in patients with various dementia disorders. [2006]

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

Omega-3 fatty acid supplementation effects on weight and appetite in patients with Alzheimer's disease: the omega-3 Alzheimer's disease study. [2015]

5. England pubmed.ncbi.nlm.nih.gov

Effect of oral administration of a whole formula diet on nutritional and cognitive status in patients with Alzheimer's disease. [2006]

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

Saturated and trans fats and dementia: a systematic review. [2018]

7. England pubmed.ncbi.nlm.nih.gov

A ketogenic diet reduces amyloid beta 40 and 42 in a mouse model of Alzheimer's disease. [2020]

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

Effect of Omega-3 Fatty Acids, Lutein/Zeaxanthin, or Other Nutrient Supplementation on Cognitive Function: The AREDS2 Randomized Clinical Trial. [2021]

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

Dietary fat composition and dementia risk. [2021]

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

High-Fat-Diet Intake Enhances Cerebral Amyloid Angiopathy and Cognitive Impairment in a Mouse Model of Alzheimer's Disease, Independently of Metabolic Disorders. [2022]

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

Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD study: a randomized double-blind trial. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Omega-3 supplementation in mild to moderate Alzheimer's disease: effects on neuropsychiatric symptoms. [2018]

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

Cerebrospinal fluid lipidomics: effects of an intravenous triglyceride infusion and apoE status. [2023]

14. 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]