The longer you use a car, a cell phone, or any other tool, the more likely it is going to break down. Parts wear out, dashboards and screens crack, and batteries die. A similar process occurs in our body, as cells and organs accumulate damage over the course of a lifetime. Despite heavy usage, it is nothing short of remarkable that the brain is able to work so efficiently for so long. But around the age of 60, signs of aging and deterioration begin to appear.

What if we could turn back the clock on the brain and reduce the cellular damage, wear and tear, and other metabolic byproducts of its heavy usage? In Alzheimer’s, glucose metabolism slows down, making it hard for brain cells to generate energy. This slowed metabolism is also linked to a build-up of amyloid plaque—one of the key biomarkers of Alzheimer’s.

Exploring whether metabolism could be the key to understanding Alzheimer’s, scientists are studying intermittent fasting—the process of switching between eating and abstaining from food on a regular schedule—and its effects on metabolism, and on the brain.

How does fasting affect the body and the brain?

There are many approaches to intermittent fasting. One of the most common, 16/8 fasting, involves eating within an eight-hour interval and abstaining from food the other 16 hours of the day. Other variations on this approach spread the timeline out, observing fasting for an entire day, or even two, each week.

In both scenarios, fasting is being used to change the body’s metabolism. When we stop eating, our bodies can no longer rely on carbohydrates and sugars for energy, and this leads to a shift. Instead, the body—brain included—begins relying on ketone bodies for energy, which are derived from fats.

When the brain shifts to ketone metabolism, brain cells enter a low-energy, protective state. Instead of creating new proteins and materials for the cell to use, these cells begin recycling existing materials through a process called autophagy—a word derived from Latin, meaning “self-eating.”

When brain cells shift into this protective, autophagous state, worn-out proteins are broken down as food, which means waste and damage within the brain are being cleared out. Scientists believe this could help prevent or slow cognitive decline by helping the cells stay healthy for longer. What could that mean for people living with Alzheimer’s?

What the evidence says about fasting and Alzheimer’s

In mouse models of Alzheimer’s, intermittent fasting may improve some of the cognitive deficits. But in humans, there are few randomized-controlled trials of fasting conditions in people with Alzheimer’s.

One reason there isn’t more research on fasting and Alzheimer’s is that there are many different types of fasting. This makes it difficult to know which type of fasting works for a particular individual. Fasting is complicated and difficult to do regularly and effectively—especially for older adults who may be experiencing cognitive decline—and that makes it difficult to replicate across large studies.

So, instead of focusing on the brain health of people who engage in fasting, some scientists are shifting their attention to ketone bodies to explore the relationship between cognitive health, brain metabolism and fasting.

An observational study in 2020 looked at 20 older adults with mild cognitive impairment — a precursor to Alzheimer’s—or other memory problems, and tailored a diet designed to turn the brain’s metabolism toward ketone bodies. After six weeks, the researchers observed, this change reduced the amount of Alzheimer’s biomarkers found in participants’ cerebrospinal fluid. Another observational study of 99 older adults with mild cognitive impairment found that intermittent fasting improved cognitive function over three years.

Mark P. Mattson, PhD, a professor at Johns Hopkins University School of Medicine, is currently conducting a clinical trial to examine the links between intermittent fasting and Alzheimer’s.

“It turns out that overeating and diabetes and insulin resistance are risk factors for cognitive impairment and Alzheimer’s disease,” Mattson explained on a podcast. His current study involves taking people at risk for cognitive impairment or Alzheimer’s with obesity and insulin resistance. Half the participants would get advice for healthy eating while the other half will fast intermittently twice a week.

If these clinical trials succeed, it may also tell us more about the underlying metabolic contributors to the disease. Combined with other lifestyle factors such as exercise and Mediterranean diet, intermittent fasting could provide even more protection against Alzheimer’s. Balanced diets and nutrition are critical to brain health. For now, speak with your doctor if you are planning on trying fasting or making other drastic changes to your diet.

To learn about clinical trials of new medications that aim to modify the pathology of Alzheimer’s disease, call Charter Research at 407-337-1000 (Orlando) or 352-775-1000 (The Villages).