What if You Could Get the Benefits of Exercise Without Working Out?

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Sept. 19, 2022 – We all know exercise is good for us. It helps you manage weight and lowers the risk of heart disease, type 2 diabetes, and even some cancers. Yet nearly half of U.S. adults don’t get the recommended 150 minutes of moderate-intensity activity a week.

Some may blame a lack of time, energy, or motivation. Others may have physical limits due to age or chronic conditions.

But what if you could achieve the benefits of exercise without breaking a sweat – by simply popping a pill or injecting medicine into your body?

That may sound too good to be true, but in fact, scientists are working toward that goal. Step one is figuring out how, on a molecular level, exercise produces health benefits. Two recent studies have advanced that field.

In Australia, a team of researchers zeroed in on changes in the muscles.

“Many of these benefits [of exercise] arise from contracting skeletal muscle,” says study author Benjamin Parker, PhD, a researcher in the Department of Physiology and Anatomy at the University of Melbourne in Australia.

The researchers collected muscle biopsies from people in the study, both before and after they did different types of exercise: endurance, sprint, and resistance training. They discovered that the same gene – called the C18ORF25 gene – was activated after all types.

When this gene was removed from mice, the result was reduced exercise capacity and muscle defects, Parker says. When it was activated, muscle function increased.

“Our study identifies C18ORF25 as a new exercise gene to promote muscle benefits,” Parker says.

The findings, reported in the journalCell Metabolism, may give us valuable insight into how to manage muscle disorders such as muscular dystrophy and myasthenia gravis, combat age-related muscle loss, and improve sport performance, Parker says.

This comes on the heels of other research from Baylor College of Medicine and Stanford School of Medicine investigating what molecules in the body exercise produces.

After analyzing blood samples from mice before and after the rodents had been running on a treadmill, the researchers found that one compound – called Lac-Phe (N-lactoyl-phenylalanine) – increased more than any other. As the level of exercise intensity increased, so did the level of Lac-Phe. Similar findings were observed in blood samples from 36 people – levels of Lac-Phe peaked after hard exercise and declined within an hour.

“We were looking for a basic biochemical understanding of the physiology of exercise and stumbled upon the discovery of Lac-Phe,” says study author Jonathan Long, MD, a biochemist at Stanford.

Lac-Phe – a byproduct of lactate (produced in large amounts during exercise) and phenylalanine (a building block for protein) – may help regulate the drive to eat, the scientists found. After being injected with the molecule, rodents that had been made obese with a special diet ate 50% less food and lost weight. (Interestingly, Lac-Phe did not have the same result when given in pill form, possibly because the digestive acids in the stomach break it down, making it ineffective.) This could explain why we don’t feel hungry right after intense exercise.

“We are actively investigating the appetite-suppressing effects of Lac-Phe and the underlying mechanisms,” says study author Yong Xu, MD, a professor of pediatrics, nutrition, and molecular and cellular biology at Baylor. If all goes well, it could be used in humans to aid weight loss someday, he says.

These are not the only studies to go after an “exercise pill.” In the past decade, researchers at Dana-Farber Cancer Institute have reported on a hormone that triggers some of the health benefits of exercise and has recently been shown to reduce levels of a protein linked to Parkinson’s disease.

Scientists from the University of Southampton in England discovered a compound that improved blood sugar levels and reduced weight in sedentary, obese mice. In other research in mice, Salk Institute scientists discovered how to activate a gene pathway triggered by running using a chemical compound. Meanwhile, the National Institutes of Health is funding a large study to investigate the molecular impact of exercise.

Still, despite the interest, it will likely be years before these findings can be turned into clinical therapies. In the meantime, if you want to reap the benefits of exercise, you’ll have to do it the old-fashioned way.

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