Can the “exercise molecule” be turned into an “exercise pill”?

Exercise changes more than 9,800 molecules in your blood, a process scientists have called a cellular “symphony.”

“You get such a dramatic change when you practice and it’s something that permeates your entire system,” Michael Snyder, chair of the genetics department at Stanford University, told me. TODAY† We think it’s a global regenerator, if you will…there aren’t that many things that can give you that.”

But not all of these molecules provide the benefits of physical activity in equal measure. Last week, researchers, mainly based at Baylor’s College of Medicine and Stanford’s School of Medicine, reported that one in particular appears to play an outrageous role. They detailed their find in the news Nature


The large team of more than two dozen scientists used a strategy called untargeted metabolomics to see what happens to molecules in the blood plasma of mice after the critters ran on a treadmill to exhaustion. Strikingly rising was a compound with the chemical formula C12huh14NO4, which the researchers then found to be N-lactoyl-phenylalanine, or “Lac-Phe” for short. The modified amino acid is synthesized from lactate (which is produced in abundance during intense exercise) and phenylalanine, one of the building blocks of proteins.

They also replicated the mouse experiment in racehorses, finding that Lac-Phe is the “most significantly induced circulating metabolite.” Later, they saw Lac-Phe levels skyrocket in 36 human volunteers as they sprinted on a bicycle, lifted weights, or cycled for endurance. The researchers noted that the data “establish Lac-Phe as one of the best exercise-regulated metabolites in humans.”

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So it seems that the blood is flooded with Lac-Phe during and after exercise, especially when it is intense. Could it perhaps be responsible for conferring some of the miraculous health effects of exercise?

Sorry, no “exercise pill”

To find out, the researchers injected obese mice with Lac-Phe, finding that it significantly reduced their appetite, reduced body fat and improved glucose tolerance over the 10-day study period. Interestingly, Lac-Phe did not confer these benefits on lean, healthy mice, even when administered at higher doses. It also didn’t work when given orally, indicating that Lac-Phe may not work as a long-sought “exercise pill.”

The researchers found further empirical support that Lac-Phe regulates the beneficial effects of exercise in a trial in which they genetically engineered mice without an enzyme key for the production of Lac-Phe. Compared to control mice, these mice without Lac-Phe lost much less weight when they followed an identical training program.

Mice administered Lac-Phe experienced no apparent adverse effects, nor did the molecule interfere with other metabolic functions, a favorable sign that human trials of the compound could begin relatively soon. Long-term studies could indicate that Lac-Phe may reduce the severity of osteoporosis, heart disease, diabetes, cognitive decline and other health problems known to be treated by exercise. While a Lac-Phe drug could never reap all the benefits of exercise, even bottling it would be a fantastic drug.

Next, the researchers want to zoom in on the effects of Lac-Phe on the brain. As they wrote:

“Future work uncovering the downstream molecular and cellular mediators of Lac-Phe action in the brain may provide new therapeutic avenues to capture the cardiometabolic benefits of physical activity for human health.”

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