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Are scientists closer to bottling the benefits of exercise in a pill?

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Research has found a molecule produced during exercise that may one day be administered to grant some benefits of working out without the effort.

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If you could take a pill to get the benefits of exercise, would that be the end of your fitness regime?

It’s a question we may be a step closer to grappling with, after researchers said they identified a molecule in the blood that is produced during exercise.

The scientists from Baylor College of Medicine and Stanford School of Medicine pinpointed the molecule, which they found could effectively reduce food intake and obesity in mice.

The idea of the research isn’t necessarily to take exercise off the menu – the researchers say it could really benefit people who are physically unable to exercise adequately.

“Regular exercise has been proven to help weight loss, regulate appetite and improve the metabolic profile, especially for people who are overweight and obese,” said one of the authors of the paper, Dr Yong Xu, a professor of pediatrics at Baylor College.

“If we can understand the mechanism by which exercise triggers these benefits, then we are closer to helping many people improve their health”.

The paper, published on Wednesday in the journal Nature, shows how mice that had been fed a high-fat diet to make them obese suppressed their food intake by about 50 per cent after being given the molecule.

From mice to men

To discover the relevant molecule, the team collected and analysed blood samples taken from mice that had been running on treadmills.

They found from exercising the mice an increased amount of an amino acid called Lac-Phe – a byproduct of the lactic acid produced through exercise – and phenylalanine, one of the building blocks of proteins.

When administered to the mice for 10 days, Lac-Phe reduced cumulative food intake, lowered body fat and improved glucose tolerance.

The team also found robust elevations in plasma Lac-Phe levels following physical activity in racehorses – and humans.

Data from the human test showed that sprinting induced the biggest increase in the molecule, followed by resistance training and then endurance training.

“Our next steps include finding more details about how Lac-Phe mediates its effects in the body, including the brain,” Xu said. “Our goal is to learn to modulate this exercise pathway for therapeutic interventions”.

“We wanted to understand how exercise works at the molecular level to be able to capture some of its benefits,” said co-author Dr Jonathan Long, assistant professor of pathology at Stanford Medicine.

“For example, older or frail people who cannot exercise enough, may one day benefit from taking a medication that can help slow down osteoporosis, heart disease or other conditions,” he said.

Long-running push for exercise pill

Identifying Lac-Phe is just the latest step in what has been an ongoing push to see whether exercise benefits could be administered in medicine.

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A 2008 study claimed to have found a substance that increased exercise endurance in mice, without the need for frequent exercise to actually take place.

The researchers at the Salk Institute for Biological Studies found that a cellular messenger system could be targeted by drugs to enhance training adaptation or even to increase endurance without exercise.

This led to the drug, known as compound 516, being branded by some as an “exercise pill”.

But one expert on inactivity at the University of Missouri, Frank Booth, said at the time it could not be considered a replacement for exercise.

That’s because the study didn’t test all of the commonly known benefits of exercise, such as increased cardiac and aerobic capacity, lower blood pressure, and decreased resting heart rate.

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A more recent study identified another protein – Sestrin – that mediates the metabolic benefits of exercise, which the scientists said “may serve as a promising therapeutic molecule for obtaining exercise-like benefits such as improving mobility and metabolism”.

Publishing the findings in the journal Nature in 2020, the researchers explained how they tested the theory successfully on flies and mice, which had different levels of sestrin.

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