In this study, the exercise tolerance of patients with AN was lower than that of healthy controls, in line with the findings of a previous study by Biadi et al . The exercise tolerance of our patients with AN was moderate-severe according to the Weber–Janicki classification , which cannot be explained by clinical factors such as BMI, duration of disease, or previous lowest weight. Age, previous minimum BMI, past duration of BMI < 15, and history of exercise were not explanatory factors contributing to the lower AT of our patients with AN.
The AT-METS of our patients with AN was 2.9 ± 0.52, suggesting that METS of approximately 2.5-3.3 is a safe intensity of physical activity for such patients. The physical activity recommendations are shown in Table 2 [22, 23]. In clinical practice, clinicians must prohibit exercise intensities that may cause further weight loss or physical complications in patients with AN. However, no index exists for teaching safe exercise intensity to AN patients at their actual physical activity level. By using AT-METS, clinicians can indicate to AN patients the exercise intensity that does not exceed the anaerobic metabolic threshold, ensuring safety. In addition, families and school educators of AN patients often ask clinicians what level of exercise intensity is acceptable for their patients.
It is particularly interesting that the decreased AT of our patients was not explained by the various clinical measures we estimated. It would be useful for clinicians to be able to estimate the exercise tolerance of their AN patients from more readily available clinical data without performing CPX. Further investigation of factors such as body composition and autonomic function test results is warranted.
The components of AT are a complex system. AT is a comprehensive metabolic index of ventilation (external respiration), circulation, and metabolism (internal respiration), defined by gas exchange, oxygen transport to skeletal muscle, and oxygen availability in skeletal muscle . Exercise performance requires an appropriate heart rate response during exercise, based on normal autonomic nervous system function . However, AN patients often have a blunted sympathetic response to maximal exercise, i.e., a variable response insufficiency (CI) . In the present study, the increase in heart rate from the start of exercise to AT was suppressed in our AN patients. In addition, the ΔHR of our patient group was shown to have a significant effect on AT. CI is associated with exercise intolerance . The autonomic abnormalities of AN patients may persist even after weight regain, and more careful management of physical activity is needed for AN patients with CI .
Reduced systolic ventricular function is not a major factor in the reduced exercise capacity of patients with AN . It has been reported that older patients have decreased oxygen availability in skeletal muscle  and decreased lean mass , both determinants of decreased exercise tolerance. However, the association between AT and muscle mass and the skeletal muscle strength of patients with AN is unclear. Another factor that may define AT is exercise habits , but this study did not show an association between exercise and AT in our AN patients. It is particularly interesting that the decreased AT of AN was not explained by the various clinical measures we estimated.
It is not advisable to manage the range of activity of patients with AN only with bed rest. In a study by Ibrahim et al, bed rest was not supported for the inpatient treatment of patients with AN . Other studies have shown that physical activity has a positive impact in the treatment of AN. Exercise and physical therapy can help AN patients recover from their physical and mental problems . Maintaining safe physical activity during the refeeding period for AN patients is beneficial for restoring body composition, maintaining bone mineral density, and mental status . Furthermore, previous studies have shown that exercise under nutritional support improves quality of life and psychological well-being . However, there is no consensus or recommendation on how physical activity should be managed in patients with AN, and implementation varies among specialized centers . The findings of the present study, which assessed the exercise physiology of patients with AN, provides an important basis for guiding the physical activity of patients with AN.
A previous study showed that the BMI percentile was independently associated with the exercise endurance of adolescents with AN . A BMI < 14 (kg / m2) was noted as an indicator of high medical risk in patients with AN , and in some institutions patients with a BMI <15 (kg / m2) are restricted from physical activity. In other centers, patients with a BMI of 18.5 < (kg / m2) are prohibited from physical activity . A BMI of 12 (kg / m2) or less has been reported to be a marker for the development of consciousness and gait disturbances . However, the BMI level of our patients with AN was not related to their AT level, indicating that the physical activity of patients with AN should not be defined and managed by BMI alone.
In conclusion, the exercise tolerance of patients with AN was lower than that of healthy controls. AN-AT was highly influenced by ΔHR, but not influenced by age, BMI, previous minimum BMI, past duration of BMI < 15, or exercise history. The AT-METS values of our AN patients with a BMI of 15.7 ± 1.8 ranged from 2.5-3.3 METS, and this index can be used by clinicians to teach AN patients a safe exercise intensity. CPX and AT-METS are useful tools for clinicians to manage physical activity in AN patients. Future research is needed to identify determinants of exercise tolerance other than CI in patients with AN.