Calorie Restriction

Unfortunately there are no studies that I am aware of that determined the cognitive effect of calorie restriction on human subjects.  However, the animal data is very promising.  Calorie restriction in animals has been shown to improve cognition, promote healthy brain aging, and prevent Alzheimer’s.  Animal studies have also shown that calorie restriction can extend life and prevent other aging related diseases. In fact, the first calorie restriction diet with an animal took place in 1935 when it was discovered that calorie restriction increased the lifespan of rats.1,3      

Even though there were no human studies that investigated calorie restriction and cognition, a few human studies focused on cardiovascular effects.  A systematic review by Caristia et al. from 2020 included eight randomized clinical trials.  In total, the trials showed a reduction of BMI, fat mass, total cholesterol, decreased LDL, and glucose and insulin levels were improved as well.4     

In animals, calorie restriction has improved cognitive scores as much as 40%.  However, the results are depending on the methods used as other calorie restriction studies have shown a decrease in cognition.  In addition, the timing of when calorie restriction is started appears to be critical.  Some (but not all) experiments that used older animals showed no cognitive effects.  Intensity and duration are also key factors.  In general, mild to moderate calorie restriction (≤40%) improved cognition when initiated in the early stages of life whereas more intense and initiation later in life reduced the effectiveness of combating age related cognitive decline.  Animal studies have also shown that calorie restriction diets can reduce amyloid plaques and improve cognition in animals that have Alzheimer’s, providing evidence that it might be beneficial in humans with Alzheimer’s.1      

There are a series of molecules that mimic the mode of action of calorie restriction.  These include drugs such rapamycin and metformin as well as natural compounds such as resveratrol, curcumin, spermidine and other SIRT activating compounds.  SIRT genes are associated with longevity and produce a group of proteins called sirtuins which are thought to be involved in the pathway that provides many of the health benefits of the calorie restriction diet.  Sirtuins have been shown in vivo to regulate lifespan and metabolic functions.  They are also involved in a process called autophagy.  Autophagy is the degradation and recycling of cellular components within cells.  Autophagy is critical to keep cells healthy, especially brain cells because autophagy is one process in which cells remove protein aggregates like amyloid-beta.  The autophagy process in Alzheimer’s patients is disrupted, so any mechanisms that can improve autophagy would be helpful.1,5,6