Fasting-Mimicking Diet for Apolipoprotein E4

Overseen By Sara Espinoza, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Cedars-Sinai Medical Center

Must not be taking: Anti-diabetics, Immune suppressants

Disqualifiers: Diabetes, Depression, Neurological conditions, others

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

Compensation: Varies

Number of Visits: 6

Duration: 6 months

60 Participants Needed

Trial Summary

What is the purpose of this trial?

The study aims to evaluate the safety, feasibility, and efficacy of six-month fasting-mimicking (FMD) intervention in middle-aged adults at elevated risk for Alzheimer's disease due to the apolipoprotein (APOE) ε4 allele. Participants randomly assigned to the active intervention will consume a FMD for 5-days each month over a period of 6-months.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are using immune suppression drugs or anti-diabetic medications, you may not be eligible to participate.

Is the Fasting-Mimicking Diet generally safe for humans?

The available research does not provide specific safety data for the Fasting-Mimicking Diet in humans, particularly in relation to the ApoE4 genetic variant or other conditions. ^{1 2 3 4 5}

How does the Fasting-Mimicking Diet treatment differ from other treatments for ApoE4-related conditions?

The Fasting-Mimicking Diet (FMD) is unique because it mimics the effects of fasting while still providing essential nutrients, potentially targeting metabolic pathways altered by the ApoE4 gene. Unlike traditional treatments, FMD focuses on a specific dietary regimen that may help reduce Alzheimer's risk in ApoE4 carriers by influencing inflammation and metabolism. ^{1 2 6 7 8}

Research Team

Mitzi Gonzales, PhD

Principal Investigator

Cedars-Sinai Medical Center

Eligibility Criteria

This trial is for middle-aged adults who are at higher risk of Alzheimer's because they carry the APOE ε4 gene. Specific eligibility criteria details were not provided, so it's important to contact the study organizers for more information on who can join.

Inclusion Criteria

BMI 20-39kg/m2 (inclusive) at screening

I carry the APOE e4 gene variant.

Stated willingness to comply with all study procedures and availability for the duration of the study

Exclusion Criteria

Has any medical disease or condition that, in the opinion of the principal investigator (PI) or appropriate study personnel, precludes study participation

I have had a gastric bypass surgery.

I have inflammatory bowel disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants in the FMD group consume a fasting-mimicking diet for 5 days each month over a period of 6 months

6 months

6 visits (in-person) after each FMD cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Treatment Details

Interventions

• FMD1

Trial Overview The NIBBLE study tests a fasting-mimicking diet (FMD) called FMD1 (LNT22-017-1), which participants follow for 5 days each month over six months. The goal is to see if this diet can improve body and brain health and potentially increase lifespan in those at risk for Alzheimer's.

Participant Groups

Group I: FMD - Intervention Experimental Treatment 1 Intervention

Participants in the FMD group will be asked to refrain from consuming any calorie-containing foods or drinks other than the provided study foods/drinks during the designated intervention days each month.

Group II: Normal Diet - Control Active Control 1 Intervention

Participants in the normal diet group will be asked to consume their regular diet.

Who Is Running the Clinical Trial?

Cedars-Sinai Medical Center

Lead Sponsor

Trials

523

Recruited

165,000+

Findings from Research

The ApoE4 allele is a significant genetic risk factor for Alzheimer's disease, and recent research has identified specific mechanisms by which it increases dementia risk, including effects on inflammation and metabolism.

A proposed precision nutrition approach for ApoE4 carriers includes a low-glycemic index diet, Mediterranean-style foods, and specific nutritional supplements, aimed at reducing Alzheimer's risk based on these mechanisms, although long-term human studies are still needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Precision Nutrition for Alzheimer's Prevention in ApoE4 Carriers. Norwitz, NG., Saif, N., Ariza, IE., et al.[2021]

In a study of female mice with human APOE3 or APOE4 genotypes, those with APOE4 showed worse metabolic health, including higher fat levels and insulin resistance, compared to APOE3 mice after 13 weeks on a control diet.

The Western diet had limited effects on both genotypes, but APOE4 mice exhibited a unique response with reduced expression of certain inflammation-related genes, suggesting that the APOE4 genotype may influence how the body reacts to dietary stressors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of APOE Genotype and Western Diet on Metabolic Phenotypes in Female Mice. Christensen, A., Pike, CJ.[2023]

In a study of 506 coronary heart disease patients, long-term adherence to a Mediterranean diet significantly reduced postprandial triglycerides in individuals with the APOE rs439401 T-allele compared to those with the CC genotype.

The findings suggest that the Mediterranean diet interacts with specific genetic variants to improve lipid profiles, indicating that personalized dietary recommendations could enhance management strategies for coronary heart disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apolipoprotein E genetic variants interact with Mediterranean diet to modulate postprandial hypertriglyceridemia in coronary heart disease patients: CORDIOPREV study. Gomez-Delgado, F., Alcala-Diaz, JF., Leon-Acuña, A., et al.[2021]

The SATgenε study successfully implemented three different dietary strategies (low-fat, high-saturated fat, and high-saturated fat with DHA) in 88 participants over 8 weeks, showing that participants could meet specific dietary fat targets effectively.

The high-saturated fat with DHA diet led to a significant increase in DHA levels in the blood, demonstrating that dietary composition can influence blood lipid profiles, regardless of the APOE genotype.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SATgenε dietary model to implement diets of differing fat composition in prospectively genotyped groups (apoE) using commercially available foods. Lockyer, S., Tzanetou, M., Carvalho-Wells, AL., et al.[2016]

A study involving 496 children over 4.4 years found that moderate dietary fat restriction does not negatively impact neurodevelopment in early childhood.

In boys, higher protein intake at age 5 and earlier cholesterol and polyunsaturated fatty acid intakes were linked to better outcomes in speech, language, and motor skills, suggesting that the quality of dietary fats and protein is important for neurodevelopment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of diet on the neurologic development of children at 5 years of age: the STRIP project. Rask-Nissilä, L., Jokinen, E., Terho, P., et al.[2013]

A 41-year-old man with progressive Huntington's disease showed significant improvements in motor symptoms (52% improvement) and daily living activities (28% improvement) after following a time-restricted ketogenic diet for 48 weeks.

The ketogenic diet also led to notable enhancements in behavior problems related to HD (50-100% improvement) and quality of life (25% improvement), with no significant adverse effects reported, indicating a potential safe dietary intervention for managing symptoms of HD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Time-Restricted Ketogenic Diet in Huntington's Disease: A Case Study. Phillips, MCL., McManus, EJ., Brinkhuis, M., et al.[2022]

A diet enriched with docosahexaenoic acid (DHA) was found to reduce spatial memory impairment in mice with the human APOE4 allele, suggesting a potential dietary intervention for cognitive issues associated with this genetic risk factor.

The study revealed that DHA consumption led to changes in brain cell morphology, specifically exacerbating reactive astrogliosis in astrocytes and enhancing the ramified morphology of microglia in APOE4 mice, indicating a complex interaction between DHA and brain immune responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A diet rich in docosahexaenoic acid enhances reactive astrogliosis and ramified microglia morphology in apolipoprotein E epsilon 4-targeted replacement mice. Chappus-McCendie, H., Poulin, MA., Chouinard-Watkins, R., et al.[2023]

Postprandial triglyceride-rich lipoproteins (TRLs) containing monounsaturated fatty acids (MUFAs) promote the polarization of microglia towards the M2 anti-inflammatory phenotype, while those with saturated fatty acids (SFAs) encourage an M1 pro-inflammatory phenotype.

This study suggests that dietary MUFAs, particularly from sources like olive oil, could be used in nutraceutical strategies to modulate microglial activity and potentially prevent neuroinflammatory diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postprandial triglyceride-rich lipoproteins promote M1/M2 microglia polarization in a fatty-acid-dependent manner. Toscano, R., Millan-Linares, MC., Lemus-Conejo, A., et al.[2021]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Precision Nutrition for Alzheimer's Prevention in ApoE4 Carriers. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Effects of APOE Genotype and Western Diet on Metabolic Phenotypes in Female Mice. [2023]

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

Apolipoprotein E genetic variants interact with Mediterranean diet to modulate postprandial hypertriglyceridemia in coronary heart disease patients: CORDIOPREV study. [2021]

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

SATgenε dietary model to implement diets of differing fat composition in prospectively genotyped groups (apoE) using commercially available foods. [2016]

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

Effects of diet on the neurologic development of children at 5 years of age: the STRIP project. [2013]

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

Time-Restricted Ketogenic Diet in Huntington's Disease: A Case Study. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

A diet rich in docosahexaenoic acid enhances reactive astrogliosis and ramified microglia morphology in apolipoprotein E epsilon 4-targeted replacement mice. [2023]

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

Postprandial triglyceride-rich lipoproteins promote M1/M2 microglia polarization in a fatty-acid-dependent manner. [2021]