Could intermittent fasting be secret to preventing Alzheimer’s disease?

LOS ANGELES — Diets that mimic fasting appear to the reduce the signs of Alzheimer’s disease, according to a groundbreaking new study using mice.

Researchers from USC Leonard Davis School of Gerontology say time-restricted eating lowered levels of two key hallmarks of the disease — amyloid beta and hyperphosphorylated tau protein. These substances build up and tangle in the brain, causing disruptions in cognitive function that lead to dementia.

The mice on this fasting diet — which were genetically-engineered to develop Alzheimer’s — also had less brain inflammation and performed better on cognitive tests than other mice fed a normal diet.

The fasting-mimicking diet (FMD) researchers examined was high in unsaturated fats and low in overall calories, protein, and carbohydrates. The diet mimics the impact of sticking to a water-only fast while still providing dieters with their necessary nutrients. Previous studies have found that fasting diets display a connection to several health benefits, including stem cell regeneration, lessening the side-effects of chemotherapy, and lowering the risk for developing cancer, diabetes, heart disease, and other age-related diseases.

How does intermittent fasting change the brain?

In this study, Professor Valter Longo and the team examined healthy mice and two groups of dementia-prone mice, E4FAD and 3xTg. Researchers fed the mice a fasting-mimicking diet for four to five days at a time, twice a month. In between these cycles, the animals ate a normal diet.

Over the long-term experiment, 3xTg mice received 30 fasting cycles over 15 months. In shorter experiments, the team fed both 3xTg and E4FAD mice anywhere from one to 12 FMD cycles over six months.

In both experiments, results reveal that mice participating in FMD cycles displayed noticeable drops in amyloid beta. This substance forms sticky plaques in the brain. Tau proteins, which form tangles in the brain, also decreased among fasting mice. The FMD group also had lower levels of brain inflammation and fewer active microglia. These immune cells seek out and destroy viruses and damaged cells throughout the brain.

The dieting mice even had lower levels of oxidative stress, which the researchers say plays a role in the onset of Alzheimer’s. Oxidative stress, which develops due to an imbalance between the production and accumulation of oxygen reactive species (ROS), damages neurons and leads to more amyloid building up in the brain. Specifically, Longo says the free radical “superoxide” plays a key role in causing damage within Alzheimer’s mouse models.

When it comes to their behavior, the study also found that fasting mice displayed less cognitive decline than their peers on a standard diet. The fasting mice performed better during a maze test in comparison to Alzheimer’s mice on a standard diet and nearly matched the performance of healthy mice.

Tests are underway among human patients

Longo and the team also reviewed data from a small Phase 1 clinical trial examining a fasting diet in human patients with mild cognitive impairment or Alzheimer’s. The 40 patients were otherwise healthy and participated in a five-day FMD once a month or simply replaced lunch or dinner with pasta or rice for five days.

The data reveals that fasting is a safe option for humans experiencing cognitive decline. Further tests hope to confirm the promising results seen among mice.

The study is published in the journal Cell Reports.

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