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Why do some people benefit more from exercise than others?

A study led by investigators at Beth Israel Deaconess Medical Center (BIDMC) is providing new insight into why the benefits of the same exercise can vary among individuals. The research could be helpful for identifying new therapeutic targets for diseases related to metabolism.

“While groups as a whole benefit from exercise, the variability in responses between any two individuals undergoing the very same exercise regimen is actually quite striking, explained study senior author Dr. Robert E. Gerszten, Chief of the Division of Cardiovascular Medicine at BIDMC.

“For example, some may experience improved endurance while others will see improved blood sugar levels. To date, no aspects of an individual’s baseline clinical profile allow us to predict beforehand who is most likely to derive a significant cardiorespiratory fitness benefit from exercise training.”

To investigate how the effects of exercise may differ from one person to the next, the researchers analyzed the blood levels of approximately 5,000 proteins in 650 sedentary adults before and after a 20-week physical fitness program.

“We were particularly interested at looking at proteins in the blood to study the effects of exercise because there is a growing body of evidence showing that exercise stimulates the secretion of chemicals into circulation that can impart their effects on distant organs,” said study first author Dr. Jeremy Robbins.

Initially, 147 proteins in the blood indicated an individual’s cardiorespiratory fitness, or VO2max. Another set of 102 proteins indicated an individual’s change in VO2max after completing the exercise program.

“We identified proteins that emanate from bone, muscle, and blood vessels that are strongly related to cardiorespiratory fitness and had never been previously associated with exercise training responses,” said Dr. Gerszten.

“Even though prior studies have shown that an individual’s baseline fitness level is unrelated to their response to exercise training, it was fascinating to see that there was minimal overlap between the protein profiles of baseline VO2max and its response to the exercise training intervention,” said Dr. Robbins.

Based on their findings, the researchers developed a protein score that predicts an individual’s trainability, or change in VO2max. This score could be used to pinpoint individuals who are unable to significantly improve their cardiorespiratory fitness. 

“Baseline levels of several proteins predicted who would respond to the exercise training protocol far better than any of our established patient factors,” explained Dr. Gerszten.

In a separate trial, the experts discovered that some of these proteins were associated with an elevated risk of premature death. This highlights the link between cardiorespiratory fitness and long-term health outcomes.

“We now have a detailed list of new blood compounds that further inform our understanding of the biology of fitness and exercise adaptation, and predict individual responses to a given exercise regimen,” said Dr. Gerszten. 

“While no pill is ever likely to recapitulate the diversity of benefits from exercise, our study has helped create a roadmap to further explore potential interventions and provides an important step in individualizing exercise as a therapy.” 

Dr. Gerszten noted that additional research is needed to better understand the precise effects of the different proteins before and after exercise.

The study is published in the journal Nature Metabolism.

By Chrissy Sexton, Staff Writer

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