Energy shortages harm the health of athletes, a new research tool shows how

In 2014, the International Olympic Committee named a syndrome that affects many of its athletes: relative energy deficits in sport, or REDs. It is now estimated that more than 40% of professional athletes have REDs, and the percentage could be even higher in recreational athletes and exercisers.

Athletes develop REDs when they consistently expend more energy through their physical activity than they consume through their diet. Over time, this prolonged energy deficit can lead to a wide range of symptoms, including hormonal and reproductive problems, insomnia and fatigue, bone weakness and injury, and a higher risk of anxiety and depression.

Despite its high prevalence, little is known about how REDs work at the cellular and molecular level – largely because there was no established laboratory model of the syndrome.

Now, researchers at the Salk Institute have created the groundbreaking mouse model of REDs and are already using it to better understand the syndrome. Their initial research found that REDs influence organ size and gene expression patterns throughout the body. Furthermore, this energy deficit appears to affect male and female mice differently: in men, kidney health was most affected, while in women, reproductive health and muscle mass were most affected.

The findings, published in Cell metabolism on September 3, 2024 to identify potential biomarkers to diagnose REDs with greater certainty and provide new molecular targets for future therapies that could halt, reverse, or prevent the syndrome altogether.

“Without an animal model of the syndrome, there was no way to understand its mechanisms at the cellular or molecular level,” said Professor Satchidananda Panda, senior author of the study and Rita and Richard Atkinson Chair at Salk.

“By establishing an effective mouse model of REDs, we can now systematically ask how the syndrome affects every organ, tissue and bone in the body and what we can do to help athletes experience these symptoms.”

Other groups have attempted to develop rodent models of REDs, but have largely failed to replicate its many symptoms. Salk scientists took a new approach and by gradually changing the animals’ exercise/food ratio, they were able to mimic many human characteristics of REDs, including high activity levels, low energy intake, reduced body weight and disrupted activity-rest patterns. and lowered blood sugar levels. They also focused on relatively young mice to model the typical age range of professional athletes, which corresponds to the age of 20-25 in humans.

“Our mouse model is an incredible milestone in ongoing research into REDs,” said Laura van Rosmalen, first author of the study and postdoctoral researcher in Panda’s laboratory. “And while it’s not great for athletes, for us scientists it’s very interesting – and shocking – to see how the entire body is affected by this syndrome.”

Using this new mouse model, the scientists measured how REDs affect the anatomy and gene expression levels of 19 different organs. Mice with REDs showed significant shrinkage of vital organs, including the kidneys and reproductive organs, and a deterioration in bone quality.

The experiments also revealed several molecular changes in the blood that could potentially be used as biomarkers to test patients for REDs – a much more effective diagnostic approach than current questionnaire-based methods.

The scientists also found several increased markers of stress in the REDs mice, including the activation of a hormone network in the brain and body known to contribute to anxiety and depression, with greater effects seen in women. What some athletes may write off as pre-race jitters, Panda adds, may actually be deeper-seated psychological changes associated with the syndrome.

The new model and initial findings emerge from Panda’s work with the Wu Tsai Alliance for Human Achievement– a collaborative team of researchers studying peak human performance and athleticism with the aim of “enabling all people to achieve optimal health and well-being” and a emphasis on female athletes.

“The recipe for health is not ‘eat less, exercise more,’” says Panda. “In fact, combining these two independently reasonable habits doesn’t seem like a good thing if you’re already healthy. But so far, the solution to REDs doesn’t seem to be as simple as increasing calorie intake. We now have a lot to explore with this model to determine exactly what our clinical recommendations should be, and I look forward to continuing that now-possible research.”

Beyond the reach of athletes, REDs can also affect others with a negative energy balance, such as people with eating disorders such as anorexia nervosa. Future research into the prevention and treatment of REDs will positively impact both these populations and athletes, promoting an overall healthier population in accordance with the mission of the Wu Tsai Human Performance Alliance.