A host of recent studies have linked exercise to improving brain and memory health, but the reasons why have remained hidden.

Now researchers at the University of California San Francisco say they’ve discovered that exercise stimulates the release of an enzyme from the liver that tells brain cells “to get young” again.

Even more exciting, the discovery may lead to a pill that reproduces the youthful benefits of exercise on the memory and the brain.

The brain support offered by physical activity is one of the most widely studied and most potent ways to defend your brain against memory problems that strike as you get older.

This newsletter is on record as calling exercise the best brain medicine there is.

Plus, as the California scientists note, exercise can improve the cognitive abilities of people at high risk of Alzheimer’s disease, frontotemporal dementia and other neurodegenerative conditions. So, even if you have a genetic profile that makes you more vulnerable to dementia, exercise can improve your condition to some degree.

Why Exercise Improves Memory

Recently in this newsletter I pointed out one reason exercise supports better brain health. It came to my attention in new research that working your muscles increases the production of the natural, anti-inflammatory substance butyrate, made by bacteria in your digestive tract.

But the California scientists have come at the question from another angle… examining changes that take place in your blood and what proteins are secreted by your liver when you exercise.

They were inspired by a study that found when the blood of young animals that exercise is transfused into older animals who rarely budge, the young blood can improve the older animals’ learning skills.

In their analyses of the blood from more active animals, they found an enzyme called Gpd1, which had never before been exhaustively analyzed. Their research revealed that Gpd1 increases in the blood after exercise and the increase goes hand in hand with improvement in the animals’ brain function.1

Added to those findings, research on humans shows that older, healthy folks who exercise also have more of this natural Gpd1 circulating in their bodies. Apparently, the liver releases extra amounts of the enzyme as a response to physical activity.

Enzyme Provided Double the Brain Benefits of Exercise

In the next step of their research, the scientists coaxed animals’ livers to produce extra amounts of Gpd1 without exercise. Three weeks of the extra Gpd1 improved the animals’ brains as much as six weeks of exercise – dramatically boosting the generation of new neurons in the hippocampus, one of the brain’s memory centers.

“To be honest, I didn’t expect to succeed in finding a single molecule that could account for so much of the benefits of exercise on the brain,” says researcher Saul Villeda. “It seemed more likely that exercise would exert many small, subtle effects that add up to a large benefit, but which would be hard to isolate. When I saw these data, I was completely floored.”

Stopping at the Blood-Brain Barrier

Interestingly, other lab tests show that Gpld1 made by the liver does not pass through the blood-brain barrier, the protective structure that keeps toxins, infectious microbes and many drugs out of the blood supply that enters brain tissue. So how does this mighty enzyme influence memory?

It appears this protein limits blood clotting and keeps inflammation in check. The researchers explain that both inflammation and the tendency of the blood to clot more easily are associated with cognitive problems and an increased risk of Alzheimer’s disease as you get older. It’s a well-known fact that poor circulation can be seen in a number of forms of dementia, from Alzheimer’s disease to vascular dementia.

New Discovery of the Liver-Brain Connection

“Through this protein, the liver is responding to physical activity and telling the old brain to get young,” Dr. Villeda says. “This is a remarkable example of liver-to-brain communication that, to the best of our knowledge, no one knew existed. It makes me wonder what else we have been missing in neuroscience by largely ignoring the dramatic effects other organs might have on the brain, and vice versa.”

Dr. Villeda also thinks that eventually Gpd1 and other proteins the body makes can be used as a pharmaceutical treatment for better brain health. “We don’t have that exercise pill right now,” he says. “This lets us know that this is a viable thing to pursue, but we’re not there yet.”2

But, he adds, his mother is excited about it!

She’s not the only one who wants to see that pill on the market soon. Meanwhile, this new research into Gpd1 gives you yet another reason to exercise daily to maintain a strong, sharp memory for years to come.


  1. https://pubmed.ncbi.nlm.nih.gov/32646997/
  2. https://www.npr.org/sections/health-shots/2020/07/09/889467347/an-enzyme-that-increases-
    with-exercise-can-improve-memory-in-mice-and-maybe-peop

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