Restoring weight is a central goal in treating anorexia nervosa, often used as a marker of medical recovery. But new research suggests that weight gain alone may not fully reflect what is happening inside the body, at least when it comes to muscle health.
In a study published in The Journal of Nutritional Physiology, researchers from the University of Arkansas examined how skeletal muscle responds to periods of calorie restriction followed by weight restoration. Using a rat model designed to mimic aspects of anorexia nervosa and recovery, the researchers found that muscle strength and quality remained impaired even after body weight returned to normal.
“In clinical studies, we usually define weight recovery as a body-mass index of 18.5 or within 95% of their age-predicted norm,” said Megan Rosa-Caldwell, an assistant professor of exercise science at the University of Arkansas and the study’s lead author. “Usually if someone is maintaining a weight above their underweight status, that is when there is not as much medical treatment.”
To explore whether weight recovery reflects full physical recovery, the researchers placed young rats on calorie-restricted diets for 30 days, followed by recovery periods of five, 15 or 30 days during which the animals could eat freely. These timeframes were chosen to approximate months to years of recovery in humans, though the authors note that translating timelines between species involves uncertainty.
The researchers assessed muscle mass, strength, and protein synthesis at each stage. They found that calorie restriction led to a 20% to 30% loss in skeletal muscle size and strength. While body weight rebounded during recovery, muscle quality did not fully return. Even after the longest recovery period, when the rats had regained and even surpassed their previous weight, muscle force relative to muscle size remained lower than in healthy control animals.
The study also found evidence that anabolic signaling pathways involved in building muscle were dampened after recovery, suggesting that the ability to rebuild muscle tissue may remain compromised. The authors wrote that “anabolic signaling cascades appear attenuated following long-term recovery,” indicating lingering changes in muscle biology.
Rosa-Caldwell cautioned that animal studies cannot fully capture the complexity of anorexia nervosa in humans. Rats do not experience the psychological dimensions of the disorder and will eat when food is available, whereas anorexia nervosa in people is often chronic, marked by relapse, and intertwined with mental health challenges.
“Musculoskeletal complications are probably lasting longer than people think and should probably be taken into consideration when we think of how to treat these individuals,” Rosa-Caldwell said.
The findings do not suggest that weight restoration is unimportant or ineffective. Rather, they highlight that weight alone may not reflect full physiological recovery, particularly when it comes to muscle health. The authors emphasize that further research is needed to determine whether similar patterns occur in humans and how treatment strategies might better support muscle recovery alongside nutritional rehabilitation.
“For me it begs the question of ‘how can we implement interventions to get the muscle back faster?’” Rosa-Caldwell said.
The authors reported that Megan Rosa-Caldwell received financial support from the National Institutes of Health. The study was supported by an NIH grant and the Arkansas Integrative Metabolic Research Center Pilot Grant as part of the AIMRC Center for Biomedical Research Excellence (COBRE) grant. The authors also acknowledged assistance from Eliza Garland, Sheridyn Pinkham, Madisyn Hancock and Sophie Jalkut.