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A short-cycle, low-calorie diet that mimics fasting appears to reduce inflammation and delay cognitive decline in mouse models
of Alzheimer's disease.
According to a new study led by the Leonard Davis College of Gerontology at the University of Southern California, a diet cycle that mimics fasting appears to reduce symptoms
of Alzheimer's disease in genetically engineered mice.
The study was recently published in
the journal Cell Reports.
The team, led by Professor Valter Longo, found that mice that underwent several cycles of a simulated fasting diet showed less Alzheimer's.
The researchers found low levels of two important features of the disease: β amyloid, the main driver of plaque accumulation in the brain, and overphosphorylated tau protein, which causes entanglement in the brain.
They also found that brain inflammation was reduced and performed better
on cognitive tests compared to rodents on a normal diet.
High in unsaturated fats and low in total calories, protein, and carbohydrates, the Fasting Simulation (FMD) is designed to mimic the effects of drinking only water while still providing essential nutrients
.
Previous research led by Longo has shown that brief cyclic fasting has multiple beneficial effects in mice and humans, including promoting stem cell regeneration, reducing chemotherapy side effects, and reducing risk factors
for cancer, diabetes, heart disease, and other age-related diseases.
In addition to healthy mice, the team also studied two mouse models of Alzheimer's disease, E4FAD and 3xTg
.
Over the course of the study, the mice were fed a simulated fasting diet twice a month for 4 to 5 days and were allowed to eat
normally between FMD cycles.
In a long-term experiment to observe the effects of old mice, 3xTg mice were placed on
a 30-cycle diet over a 15-month period.
Short-term experiments in 3xTg and E4FAD mice ranged from one FMD cycle to 12 cycles
over 6 months.
In both models, mice undergoing FMD cycles showed promising reductions
in β amyloid (which forms sticky, destructive plaques in the brain) and tau protein pathology compared to mice that ate a standard diet.
Mice with FMD also showed lower levels of brain inflammation, including a reduced number of active microglia, immune cells that seek out and destroy pathogens, and damaged cells
in the brain.
In addition, mice that ate this food showed lower levels of oxidative stress, which plays a role
in the pathology of Alzheimer's disease by damaging neurons and promoting the accumulation of amyloid in the brain.
Longo explained that the study specifically points to free radical "superoxide" as the main culprit for damage in mouse models of Alzheimer's
.
On the surface, the two Alzheimer's model mice that received FMD had less
cognitive decline than the control mice on the standard diet.
Cognitive behavior, including exploration and performance in the maze, was tested in young mice
before the start of the diet regimen and again after a standard diet of several months or a two-month FMD cycle.
Alzheimer's mice fed FMD performed significantly better than Alzheimer's mice fed a standard diet, and in some cases behaved similarly to control mice that were less prone to Alzheimer's, suggesting a marked slowdown
in cognitive decline.
In the two main mouse models of Alzheimer's disease, the FMD cycle appeared to effectively reverse a range of pathological markers, but also cognitive deficits
.
Longo said the results are
promising.
In addition to the study in mice, Longo and his colleagues collected data from a small phase I clinical trial conducted in human patients diagnosed with mild cognitive impairment or mild Alzheimer's
.
Forty healthy patients with family support were randomly divided into two groups, one on a monthly, 5-day simulated fasting diet, and the other on a 5-day diet
with pasta or rice instead of lunch or dinner.
Preliminary data suggest that FMD is safe and viable
for patients with mild impairment or early Alzheimer's disease.
Further testing from ongoing clinical trials will measure cognitive performance, inflammation and more
, Longo said.
Other early trials of this diet published by Longo and colleagues have also shown other benefits of once a month, such as reducing fat mass without losing muscle mass and improving cardiometabolic risk factors, especially in
people who are overweight or obese.
Notably, in a recently published clinical trial co-authored by Longo, FMD cycles were associated
with disease regression in people with diabetes.
According to the Alzheimer's Association, diabetes nearly doubles
the risk of developing Alzheimer's.
