5 days a month! New study shows that mimicking fasting diet cycles can improve Alzheimer’s disease

Alzheimer’s disease is one of the deadliest diseases in the world, and it is difficult to prevent, cure or even slow its progression. According to the survey results of the “China Alzheimer’s Disease Report 2021”, the prevalence and mortality of AD in China are slightly higher than the global average, and the relevant data in women is higher than that in men.

The 93rd Academy Awards Best Picture “Father Trapped in Time” is a movie about Alzheimer’s patients, which is based on Alzheimer’s patients From the main perspective, images are used to reproduce the completely gelatinized substances in the minds of Alzheimer’s patients.

Father Trapped in Time Poster

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by the hyperphosphorylation of tau protein by amyloid-beta (Aβ) and fibrillary tangles are formed in ways that alter kinase and phosphatase activity. This unique neuropathology can lead to inflammatory and oxidative damage, synaptic degeneration, and neuronal death, ultimately affecting learning and memory functions in the cerebral cortex and hippocampus.

Mimicking fasting-diet cycles appears to delay pathological progression in mice with Alzheimer’s disease, according to a new study led by the USC Leonard Davis School of Gerontology. Improve their cognitive behavior.

doi: 10.1016/j.celrep.2022.111417

You may be wondering, what is an imitation fasting diet?

Fasting-mimicking diet (FMD) is a low calorie/low protein but high unsaturated fat diet that is resistant to stress or The effects of longevity-related indicators are similar to those caused by pure water fasting, but it minimizes the burden of long-term fasting because it provides nutrients and trace elements.

In this study, the researchers fed mice two FMD formulas, a day 1 diet and a day 2-4/5 diet. The diet on day 1 consisted of approximately 55% fat, 36% carbohydrate and 9% protein, and the intake of mice ranged from 12.36kJ to 17.31kJ. The diet on days 2-4/5 consisted of approximately 43.3% fat, 47.4% carbohydrate and 9.3% protein, and the daily intake of mice ranged from 8.17kJ to 11.44kJ.

The researchers selected two transgenic mouse models, 3xTg and E4FAD. The 3xTg AD mouse model has both Aβ and tau protein pathological manifestations, which is similar to that of human Alzheimer’s disease patients. The pathological manifestations are similar, and the E4FAD mouse model can express the human ApoE4 genotype. ApoE4 carriers are of great significance for the study of Alzheimer’s disease treatment. Mice were given two 5-day imitation fasting diet cycles per month. Both the control group and the FMD interval were fed according to rodent diet standards. After several cycles, mice in both models were tested separately.

Bi-monthly cycles of FMD improved both transgenic mice after baseline behavioral tests, including Spontaneous Alternating Behavior (SAB) and Elevated Plus Maze (EPM), and the Barnes Maze Test Models of visual attention, working memory, and spatial memory can simultaneously improve anxiety behavior and increase exploratory activity.

Tig3. SAB scores in two mouse models

Follow-up pathological studies found that two mouse models that went through the FMD cycle had reduced expression levels of key pathological markers of AD, including Aβ and hyperphosphorylated tau, as well as small Glial cell density and neuroinflammatory markers, by which to improve cognitive function in mice. Part of the reason for this may be by modulating the activities of microglia and macrophages to exert protective functions, including clearance of Aβ, while reducing the production of toxic O2-/ONOO-.

Tig4. The main representative pictures of the immune responses of the two mouse models

The study also found that Egr(1-4) gene expression was down-regulated in the cortex of 3xTg mice in the FMD group compared with the 3xTg control group. In mammals, the expression of Egr1 is mainly upregulated by the energy sensor AMPK, and Egr1 itself is also in low-calorie conditions.Or activated by drugs such as metformin. In the nervous system, Egr1 downregulation is associated with reduced inflammation and pathological manifestations, and inhibition of Egr1 expression by siRNA or drugs may reduce microglial activation and may alleviate neuroinflammation caused by AD.

It can be seen that a diet cycle that mimics fasting can effectively improve the clinical manifestations of AD mice and delay their pathological progression.

So, is the FMD diet cycle safe and effective in human patients?

To assess the feasibility and safety of performing an FMD cycle in patients diagnosed with amnestic mild cognitive impairment (aMCI) or mild AD, researchers A phase I/II randomized controlled (single-blind) clinical study was initiated to test the effects of monthly FMD cycles in 40 nutritionally well-established patients with aMCI or mild AD. The results suggest that in patients with aMCI or mild AD, it is generally safe to perform monthly 5-day cycles of FMD. However, this result still needs to be supported by large-scale clinical studies and data, and it is still necessary to clarify whether the FMD cycle can really delay the cognitive decline of such patients, delay the transformation of aMCI patients to AD, and affect the expression of related biomarkers.

In conclusion, a fasting-diet-mimicking eating cycle may be safe in well-nourished patients with mild amnesic cognitive impairment or mild Alzheimer’s disease. This dietary cycle can improve patients’ cognitive function and delay disease progression. In the future, this may become a new direction for the clinical treatment of such patients.


1. China Alzheimer’s Disease Report 2021

2. Rangan, Priya et al. “Fasting-mimicking diet cycles reduce neuroinflammation to attenuate cognitive decline in Alzheimer’s models.” Cell reports vol. 40,13 (2022): 111417. doi: 10.1016/j.celrep.2022.111417

Writing | A Wool

Editing|Little Ears