Anorexia nervosa may result in long-term skeletal muscle impairment

Anorexia nervosa is a psychiatric condition characterized by a fear of weight gain and reduced calorie consumption that can result in dangerous weight loss. This condition is thought to affect around 1-4% of all women, and those who suffer from it, or have suffered from it, are estimated to be three times more likely to die prematurely than those who have never had it.  

Anorexia nervosa (or AN) doesn’t just result in fat loss. It can also result in a 20-30% loss of skeletal muscle strength and size, which is critical to longevity and the ability to do basic activities like grocery shopping or picking up babies. Along with treating the psychiatric component, a standard goal of treating AN is to restore 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,” explains Megan Rosa-Caldwell, an assistant professor of exercise science at the University of Arkansas who specializes in muscle biology. “Usually if someone is maintaining a weight above their underweight status, that is when there is not as much medical treatment.”  

But is gaining lost weight an ideal indicator of restored health? A recent study published in the Journal of Nutritional Physiology suggests that muscle impairment persists even after weight recovery. The study was led by Rosa-Caldwell using rat models. 

THE STUDY 

To model shorter- and longer-term recovery periods, eight-week-old rats were placed on calorie-restricted diets for 30 days. Eight weeks was an attempt to approximate the relatively young age at which AN usually manifests in humans, usually between adolescence and early adulthood. The rats were then examined after five days of recovery, 15 days and 30 days, during which they were allowed to eat as much as they liked (one cohort was also studied immediately after the initial 30-day experiment).  

The five and 15-day timelines were selected to simulate five and 15 months, respectively, of recovery in human age, which corresponds to common in-patient and out-patient treatment times. Thirty days corresponds to two-three years in humans. (Rats live roughly 22 months compared to 70-plus years for humans, so there is some guesswork involved.) 

The researchers then conducted a series of tests to assess muscle mass, strength and protein synthesis rates. Perhaps the most significant finding was a roughly 20% reduction in muscle size and loss of strength. These changes to muscle health did not change with shorter term recovery (both the five- and 15-day timelines). Even after 30 days, by which time the animals had returned to their earlier weight and even “caught up” to healthy control rats, there was an overall decrease in muscle quality, resulting in lower muscle force per unit of muscle mass.  

The researchers also found evidence of changes in protein synthetic signaling, stating that “anabolic signaling cascades appear attenuated following long-term recovery from AN.” Translation: the ability to build muscle had been weakened.  

IMPLICATIONS FOR TREATMENT OF AN 

According to Rosa-Calwell, the upshot is “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.” 

While parallels between humans and rats can only provide so much insight, Rosa-Caldwell thinks the effects of AN on rats are probably less severe than in humans due to the controlled nature of the experiment. Rats don’t suffer low self-image and will eat more if allowed. In humans, AN is often a decades-long struggle, with the time between diagnosis and sustained recovery often lengthened by periods of relapse. By some estimates, only around 50% of individuals achieve sustained recovery. As such, AN may represent one of the more persistent causes of muscle atrophy. 

Rosa-Caldwell concludes, “For me it begs the question of ‘how can we implement interventions to get the muscle back faster?’” 

Rosa-Caldwell’s co-authors on the study included Lauren Breithaupt, Ursula B. Kaiser, Ruqaiza Muhyudin, and Seward B. Rutkove.