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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a diet that mimics fasting can benefit individuals at higher risk of Alzheimer’s due to a specific gene. Participants will either maintain their normal diet or follow the Fasting-Mimicking Diet (FMD) for five days each month over six months. The trial aims to determine if this diet is safe and effective in reducing Alzheimer's risk. It is suitable for individuals aged 45-65 who carry the APOE ε4 gene and have a body mass index (BMI) between 20 and 39, without major health issues or dietary restrictions. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could potentially lower Alzheimer's risk.

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.

What prior data suggests that this fasting-mimicking diet is safe?

Research shows that fasting-mimicking diets (FMDs) are generally safe. Studies have found that FMD cycles are both feasible and safe for a small group of patients with Alzheimer's disease, allowing them to follow the diet without major issues. The diet consists of plant-based foods, which are safe to consume.

Additionally, the FMD has been shown to aid in weight management and improve overall health, indicating good tolerance. Another study found that the FMD can reduce inflammation in the body, benefiting health. Evidence from other studies confirms the diet's safety for humans. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Fasting-Mimicking Diet (FMD) for individuals with the Apolipoprotein E4 variant because it offers a novel approach to managing metabolic and neurological health. Unlike standard treatments that typically involve medication or lifestyle changes, FMD mimics the effects of fasting while still allowing food intake, which may help improve cellular health and reduce inflammation. This diet approach could potentially lead to benefits in brain health, which is particularly relevant for those with the ApoE4 gene, associated with a higher risk of Alzheimer's disease. By potentially altering metabolic pathways without the need for drugs, FMD represents a promising alternative or complement to existing therapies.

What evidence suggests that the Fasting-Mimicking Diet might be an effective treatment for Alzheimer's risk?

Research has shown that fasting-mimicking diets (FMDs) might help prevent and treat Alzheimer's disease, particularly in individuals at risk due to the APOE ε4 gene. Studies with mice demonstrated that FMD cycles can slow memory loss and reduce Alzheimer's signs. These diets also lower brain inflammation, which is linked to Alzheimer's. In humans, FMDs have shown promise in improving overall health and reducing the risk of long-term diseases. In this trial, participants in the FMD group will follow a fasting-mimicking diet regimen, while those in the control group will maintain their normal diet. This suggests that fasting-mimicking diets could effectively slow or prevent Alzheimer's in at-risk individuals. ^{1 4 5 6 7}

Who Is on the Research Team?

Mitzi Gonzales, PhD

Principal Investigator

Cedars-Sinai Medical Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10377404/

The Potential of Fasting-Mimicking Diet as a Preventive ... This review examines the potential of fasting-mimicking diets (FMDs) in preventing and treating Alzheimer's disease (AD).

2. cell.com cell.com/cell-reports/fulltext/S221112472201258X

Fasting-mimicking diet cycles reduce neuroinflammation to ... Here, we show that FMD cycles reduce cognitive decline and AD pathology in E4FAD and 3xTg AD mouse models, with effects superior to those caused ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2211124719301810

Fasting-Mimicking Diet Modulates Microbiota and ... Our results indicate that FMD cycles cause a reduction in intestinal inflammation, increase intestinal stem cells (ISCs), and promote the ...

4. uclahealth.org uclahealth.org/news/article/fast-track-health-inside-fasting-mimicking-diet

Fast track to health? Inside the Fasting Mimicking Diet In recent studies Link is external, the FMD has shown promising results in weight management, metabolic health, and chronic disease risk ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06115551?term=AREA%5BBasicSearch%5D(fasting%20mimicking%20diet)&rank=1

NCT06115551 | Fasting Mimicking Diet and Autophagy This study aims to evaluates autophagy in circulating white blood cells from generally healthy human volunteers exposed to fasting mimicking diet (FMD), a 5-day ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05698654

Fasting-mimicking Diet and Longevity Diet, Body ... The fasting-mimicking diet consists of a blend of 100% plant based nutrients generally regarded as safe. The formulation of these products is based on studies ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6528490/

Fasting-Mimicking Diet Modulates Microbiota and Promotes ... They also show that a similar FMD is safe, feasible, and effective in reducing systemic inflammation and the consequent high levels of immune cells in humans.