Diet, Alzheimer’s, and Protecting the Brain
A recent study found that a diet that mimics fasting protects the brain of mice against Alzheimer’s Disease
There is a large body of literature on dietary modifications that have a beneficial effect on aging and aging-associated diseases, including Alzheimer’s Disease. A recent study added to this important literature by analyzing the effect of a diet that mimics fasting in a mouse model of Alzheimer’s Disease. Here is the study:
These researchers at the University of Southern California fed Alzheimer’s Disease model mice either normal mouse chow or a fasting-mimicking diet for five days two times each month beginning at 3 months of age.
The fasting mimicking diet improved a variety of cognitive measures in the mice, reduced levels of amyloid beta and inflammatory cytokines, and increased markers of neurogenesis. In other words, a variety of positive changes were seen in the mice placed on the fasting-mimicking diet.
One of the beneficial changes seen in the mice on the fasting-mimicking diet was reduced activation of microglia, which I previously noted are associated with inflammation and neurodegeneration:
Thus, the fasting-mimicking diet was able to reduce neuroinflammation, which is associated with poor brain health.
The authors speculated that superoxide, a type of reactive oxygen species (ROS) associated with worse outcomes in Alzheimer’s Disease, might be a key factor in the effect of the fasting-mimicking diet.
They examined expression of the enzyme NOX2, which produces superoxide. They found that the fasting-mimicking diet indeed suppressed expression of NOX2. They then genetically deleted NOX2 in the Alzheimer’s model mice and found a protective effect similar to what was seen in mice who were given the fasting-mimicking diet.
The authors then tested the feasibility of using a fasting-mimicking diet in humans. They enrolled 28 patients with mild cognitive impairment or mild Alzheimer’s Disease in a study to test whether the diet would be possible in human patients. Here are the interesting details of their diet study in humans:
“The placebo diet assigned to patients in the control arm consists of replacing lunch or dinner with a meal based on pasta or rice with vegetables for 5 days a month, without supplements, whereas patients in the FMD arm complete FMD cycles that last 5 days, with supplements noted for fasting-mimicking, neuroprotective, anti-inflammatory, and antioxidant properties, including olive oil, coconut oil, algal oil, nuts, caffeine, and cocoa, given to patient in between FMD cycles for 25 days and while on a normal diet.”
Five of the 12 patients in the fasting-micking diet dropped out of the study after four cycles for a variety of reasons. But 5 of the 16 patients on the placebo arm also dropped out, perhaps indicating this is the expected dropout rate in a dietary study.
Thus, a fasting-like diet for 5 days each month seems to be reasonably well tolerated in humans, and was beneficial in mice, so might be an exciting new option for Alzheimer’s patients.
I should also note that my lab previous showed that NOX enzymes promote ferroptosis:
Given the protective effect of NOX2 knockout in the Alzheimer’s mice, and the fact their fasting-mimicking diet involved giving olive oil, which is high in oleic acid, an inhibitor of ferroptosis, I can’t help but wonder whether the fasting-mimicking diet is beneficial, at least in part, because it suppresses ferroptosis.
