Cycles of a fasting-mimicking diet appear to reduce markers of Alzheimer’s disease in mice genetically engineered to develop the disease, according to a new study led by the Leonard Davis School of Gerontology at the University of Southern California.
The study appeared in cell reports On September 27.
The researchers, led by Professor Walter Longo in collaboration with Professors Christian Pike and Pinchas Cohen, found that mice that underwent several cycles of a fasting simulation regimen showed fewer Alzheimer’s disease pathologies. The researchers found lower levels of two hallmarks of the disease: beta-amyloid – the primary driver of plaque buildup in the brain – and hyperphosphorylated tau protein, which forms tangles in the brain. They also found that encephalitis decreased and performed better on cognitive tests compared to mice fed a standard diet.
The Fasting Mimicking Diet (FMD) is high in unsaturated fats, low in total calories, protein, and carbohydrates, and is designed to mimic the effects of water-only fasting while providing essential nutrients. Previous research led by Longo indicated that short and periodic FMD cycles are associated with a range of beneficial effects, including enhancing stem cell regenerationreduce Side effects of chemotherapyAnd the Reduce risk factors For the treatment of cancer, diabetes, heart disease, and other age-related diseases in mice and humans.
Promising results in mouse models of Alzheimer’s disease
Besides healthy mice, the team examined two mouse models of Alzheimer’s disease, E4FAD and 3xTg. During the study, mice were fed a diet that simulated fasting for 4 or 5 days twice a month and allowed to eat normally between FMD cycles. In a long-term trial to see the effects in elderly mice, 3xTg mice were placed on the diet for 30 cycles in 15 months. Short-term trials in both 3xTg and E4FAD mice ranged from one FMD cycle to 12 cycles at 6 months.
In both models, mice that underwent FMD cycles showed promising decreases in beta-amyloid — which forms the sticky and destructive plaques in the brain — and tau pathology compared to mice on a standard diet. The FMD mice also showed lower levels of encephalitis, including a decrease in the number of active microglia, the immune cells that search for and destroy pathogens and damaged cells in the brain. Additionally, mice on the diet showed a lower level of oxidative stress, which plays a role in Alzheimer’s disease by damaging neurons and contributing to amyloid buildup in the brain. Longo explained that the study pointed to free radicals, “superoxide,” as the main cause of damage in mouse models of Alzheimer’s disease.
Ostensibly, mice from both Alzheimer’s disease models that succumbed to FMD showed lower cognitive decline than their counterparts on the standard diet. Cognitive behavior, including exploration and performance within mazes, was tested in young mice before the start of the diet and again after several months of either a standard diet or twice-monthly cycles of FMD. Mice with Alzheimer’s disease, given FMD, significantly outperformed Alzheimer’s mice on a standard diet, and in some cases their performance was similar to that of mice without Alzheimer’s disease, indicating that cognitive decline was significantly slowed.
FMD cycles appeared to be effective in reversing a range of pathological signs as well as cognitive defects in two major mouse models of Alzheimer’s disease. Longo said the results are promising.
Small clinical study explores feasibility for humans
In addition to the study in mice, Longo and colleagues also included data from a small phase 1 clinical trial of the fasting-mimicking diet in human patients diagnosed with mild cognitive impairment or mild Alzheimer’s disease. Forty patients who were otherwise healthy and had family support were randomly assigned to either a fasting-mimicking diet once per month or for a 5-day period or a 5-day period in which lunch or dinner was replaced by a pasta- or rice-based meal.
Preliminary data indicate that FMD is safe and feasible for patients with mild impairment or early Alzheimer’s disease. Longo said more tests in the ongoing clinical trial will measure cognitive performance, inflammation, and more.
Other early trials of the diet published by Longo and colleagues indicated other benefits of PMS, such as losing fat mass without losing muscle mass and improving cardiac metabolic risk factors, especially in people who are overweight or obese.
Notably, in a Recently published clinical trials Where Longo was a co-author, FMD cycles were associated with disease regression in people with diabetes. Diabetes almost doubles the risk of Alzheimer’s disease Alzheimer’s Association.
Other authors include first authors Priya Ranjan, Flor Lobo, and Eduardo Parilla from the University of Southern California. Terry Lee Stephen, Christian J. Pike, Pinchas Cohen, Kyle Shea, Catelyn Tran, Brandon Ann, and Dolly Choudhury of the University of Southern California; Anna Laura Cremonini, Luca Tagliafico, Angelica Percia, Irene Cava, Fiammetta Monacelli, Patrizio Odetti, Tommaso Bonfiglio and Alessio Nuncioni from the University of Genoa, Italy; Nicholas Rochet, Marco Morcelli, and Matteo Pellegrini from UCLA; Mary Jo Ladeau of the University of Illinois at Chicago; and Martina Pigliautile, Virginia Boccardi, and Patrizia Mecocci from the University of Perugia, Italy.
The study was funded in part by NIH/National Institute on Aging grants AG20642, AG025135, and P01 AG034906 to Longo; AG058068 to pike; NIA T32 AG052374 Training Scholarship to Rangan; and grants PE-2016-02362694 and PE-2016-02363073 given by the Italian Ministry of Health to Odette, Micucci, Monacelli and Lungo. The LaDu Laboratory is funded by NIH (NIA) R01 AG056472, R01 AG057008, UH2/3 NS10012, R56 AG058655, 1R44 AG060826, institutional funds from the University of Illinois College of Medicine, Chicago, and generous charitable contributions.
Longo is the founder of L-Nutra and has an ownership stake in; The company’s nutritional products are used in fasting-mimicking diet studies. Longo’s interest in L-Nutra is disclosed and managed in accordance with USC’s Conflicts of Interest policies. USC has an ownership interest in L-Nutra and the ability to receive royalty payments from L-Nutra. USC’s financial interest in the Company is disclosed and managed under USC’s Corporate Conflicts of Interest policies.
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