Anorexia nervosa is a psychiatric disorder marked by an intense fear of gaining weight and reduced calorie intake, leading to significant weight loss. It affects approximately 1-4% of women and is associated with a threefold increase in the risk of premature death compared to those who have never experienced the condition.
Beyond fat loss, anorexia nervosa also leads to substantial reductions in skeletal muscle strength and size—by as much as 20-30%. This muscle loss can impact basic activities such as grocery shopping or lifting children. Standard treatment for anorexia nervosa includes addressing psychological symptoms and restoring lost weight.
"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, assistant professor of exercise science at the University of Arkansas specializing in muscle biology. "Usually if someone is maintaining a weight above their underweight status, that is when there is not as much medical treatment."
However, new research published in the Journal of Nutritional Physiology suggests that regaining lost weight may not fully restore health. The study was led by Rosa-Caldwell using rat models to simulate both short-term and long-term recovery periods after calorie restriction.
Eight-week-old rats were placed on calorie-restricted diets for 30 days to mimic the onset age typical in humans with anorexia nervosa—adolescence to early adulthood. After this period, rats were allowed unrestricted food access and evaluated after five days, fifteen days, and thirty days—the latter representing up to two or three years in human terms due to differences in lifespan between species.
Researchers measured muscle mass, strength, and protein synthesis rates throughout these recovery phases. They found about a 20% reduction in muscle size and strength following calorie restriction—a deficit that did not improve during shorter-term recovery (five or fifteen days). Even after thirty days—when rats had regained their previous weights—the overall quality of muscle remained diminished, resulting in lower force production per unit mass compared with healthy controls.
The team also observed changes in protein synthetic signaling pathways: "anabolic signaling cascades appear attenuated following long-term recovery from AN." This means the ability to rebuild muscle was weakened even after apparent physical recovery.
According to Rosa-Caldwell: "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 noted that while animal models provide important insights into disease mechanisms, results may underestimate severity seen in humans due to differences such as psychological factors affecting eating behavior. In people with anorexia nervosa, relapse often extends the time between diagnosis and sustained recovery; only about half achieve lasting remission according to some estimates. As a result, anorexia nervosa may be one of the more persistent causes of ongoing muscle atrophy.
"For me it begs the question of 'how can we implement interventions to get the muscle back faster?'" concluded Rosa-Caldwell.
Co-authors on this study included Lauren Breithaupt, Ursula B. Kaiser, Ruqaiza Muhyudin, and Seward B. Rutkove.
