Lingering Muscle Damage After Weight Restoration in Anorexia Nervosa May Require Long-Term Care

Weight restoration is traditionally recognized as the central indicator of recovery in those with anorexia nervosa (AN); however, recent studies are discovering that attaining normal weights may not necessarily reflect full physiologic recovery. In fact, recent studies are showing that there is skeletal muscle depletion that occurs in these patients long after they attain their clinically defined weight of recovery.¹

Defining Weight Recovery Versus Functional Recovery

In clinical practice, weight recovery is commonly used as a benchmark for improvement in AN, but this metric may oversimplify the complexity of recovery. “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.”¹

Notably, emerging research has suggested that while fat mass could potentially return when a patient’s diet would allow for refeeding, a deficit in skeletal muscle mass can persist.^1,2 This has important practical implications for several reasons, including that skeletal muscle is important for a patient’s mobility, strength, metabolism, and immune system, as well as medication pharmacokinetics. A deficit can lead to a risk for a patient’s vulnerability to weakness, injury, or decreased physiological resilience, regardless of whether a weight target has been achieved.

Muscle Atrophy as a Consequence of Prolonged Malnutrition

AN is a state of chronic energy deficiency inducing widespread catabolism of lean body mass. Previous studies have demonstrated that malnutrition in AN causes a profound loss of both peripheral and axial skeletal muscle, due to a reduction in protein synthesis and an increase in protein breakdown.³ These changes involve not only the quantity of muscle but also its quality, reflected by changes in muscle fiber composition and mitochondrial function, which may take substantially longer to recover than body weight alone.

Recent research and clinical data show that pathways for muscle regeneration may be persistently impaired despite an enhancement of nutritional intake.^1,2 This may explain symptoms of muscle weakness, reduced exercise capacity, or functional impairment in patients despite showing improvement on the recovery scale. According to Rosa-Caldwell, the upshot is that “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.”¹

Where’s the Disconnect Between Refeeding and Muscle Restoration?

While it is true that nutritional restitution is necessary to sustain life, it may not be enough to reinstate muscle tissue. The study, published in The Journal of Nutritional Physiology, reveals that muscle protein synthesis fails to respond normally to adequate caloric intake, especially when an individual has starved.² Additionally, other variables like endocrine disorders, inflammation, or neuromuscular junction disorders could still impair muscle tissue repair.

This implies a disconnect in the models of treatments today, which minimize clinical care when weight goals have been accomplished. Patients may get discharged from an intensive care setting before functional recovery has taken place, and such long-term complications may not be identified or addressed. Rosa-Caldwell highlights this gap, concluding, “For me it begs the question of ‘how can we implement interventions to get the muscle back faster?”¹

How Can the Pharmacist Support Comprehensive Recovery?

Pharmacists are well positioned to help bridge the gap between weight recovery and functional recovery in AN. Pharmacists can assist in monitoring those medications that may have an additional effect on muscle function, which may include the use of corticosteroids or those that may involve the regulation of electrolytes. They can further inform patients about the right intake of protein or the number of amino acids needed for muscle restoration. Vitamin D and zinc are examples of those that may be required.

In addition, pharmacokinetic processes related to the absorption and distribution of drugs could be assessed by pharmacists. This may be a consideration for patients with a decreased lean body mass. It is possible the pharmacokinetic process of certain drugs could be affected when muscle mass is a consideration. The awareness of a deficit in muscle mass could lead to closer monitoring of a patient.

Rethinking Long-Term Management Strategies

A recognition that there is a disparity in recovery compared to weight normalization may require more than just follow-up care. Adding elements of resistance training, physical therapy, or tailored nutrition plans may be an important step to achieve muscle recovery.^1,2 Pharmacists, as members of an accessible healthcare team, may contribute to enforcing plans for following up treatment and referring patients for care beyond recovery.

Ultimately, these findings challenge the notion that weight alone is an adequate endpoint for recovery in AN. Persistent muscle damage may represent an underrecognized contributor to relapse risk and long-term morbidity. By expanding the definition of recovery to include functional and musculoskeletal health, clinicians—including pharmacists—can help support more durable, holistic outcomes for patients.

REFERENCES

1. Anorexia nervosa may result in long-term skeletal muscle impairment. EurekAlert! Published January 5, 2026. Accessed January 7, 2026. https://www.eurekalert.org/news-releases/1111559

2. Rosa-Caldwell ME, Breithaupt L, Kaiser UB, Muhyudin R, Rutkove SB. Changes in muscle strength and moderators of protein turnover in a rodent model of anorexia nervosa and recovery. The Journal of Nutritional Physiology. 2025;4:100010. doi:https://doi.org/10.1016/j.jnphys.2025.100010

3. Garrido EM, Lodovico LD, Dicembre M, et al. Evaluation of muscle-skeletal strength and Peak-Expiratory-Flow in severely malnourished inpatients with anorexia nervosa: a pilot study. Nutrition. Published online January 2021:111133. doi:https://doi.org/10.1016/j.nut.2020.111133