Author Response: High Protein but Normocaloric Diet in the ICU does not Prevent Muscle Atrophy due to Immobility

We thank the correspondent for their interest in our work and for raising thoughtful comments on our recently published study on the effect of high-protein normocaloric nutrition (HPNCD) on skeletal muscle wasting in critically ill mechanically ventilated patients during the 1st week of intensive care unit (ICU) stay. 1 We address each of the concerns raised below:We agree that in healthy athletes, increases in muscle mass typically require both adequate protein intake and resistance training.However, critically ill ICU patients represent a fundamentally different physiological state.In this context, rapid muscle catabolism is driven by inflammation, immobility, and hormonal/metabolic dysregulation.Protein provision in this setting may help reduce net catabolism by increasing substrate availability for protein synthesis, even in the absence of training.Several ICU studies have demonstrated that increased protein delivery, even without exercise, attenuates-but does not abolish-loss of lean body mass. 2 We did not claim that protein alone reverses ICU-acquired weakness, but rather that it may mitigate its severity during the acute phase.Our results demonstrate statistically significant attenuation of muscle loss in the HPNCD group, which we cautiously interpreted as "prevention" in relative terms, not absolute muscle preservation.While age-related sarcopenia is well recognized, evidence suggests that older critically ill patients can still benefit from adequate protein provision. 3Furthermore, the median age of our patients in both groups was around 36 years, and only 1 patient was above the age of 60 years.We acknowledge that baseline muscle mass may differ by age, but this was not the focus of our study, which examined within-patient changes over time.Our trial was explicitly designed as an exploratory, single-center randomized controlled trial (RCT) to generate preliminary data.We have clearly acknowledged the small sample size and the need for larger, multicenter studies to confirm these findings.As is common in pragmatic ICU nutrition trials, our cohort included patients with varied primary diagnoses.Both groups were well-matched at baseline with respect to age, sex, comorbidities, and severity scores (SOFA, APACHE-II, NUTRIC).The heterogeneity in diagnoses reflects actual ICU practice, where nutrition interventions apply across mixed critical illnesses.Preadmission activity level is indeed a potential confounder; unfortunately, this information is difficult to reliably obtain in acutely ventilated patients.However, random allocation makes systematic imbalance between groups in prior activity levels unlikely.Admission diagnoses were documented in Table 1 of our article. 1Pneumonia was the most common cause, but other conditions