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• W3108379747 abstract "We congratulate McNelly et al1McNelly A.S. Bear D.E. Connolly B.A. et al.Effect of intermittent or continuous feed on muscle wasting in critical illness: a phase 2 clinical trial.Chest. 2020; 158: 183-194Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar for performing a single-blinded multicenter randomized controlled trial, described in CHEST (July 2020), that answered an important question with significant implications for the quality of life of critically ill patients with multiorgan failure. McNelly et al1McNelly A.S. Bear D.E. Connolly B.A. et al.Effect of intermittent or continuous feed on muscle wasting in critical illness: a phase 2 clinical trial.Chest. 2020; 158: 183-194Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar demonstrated that skeletal muscle wasting was not prevented by intermittent feeding (IF), as compared with continuous feeding (CF), in early critical illness. We wish to propose a slight deviation from the main conclusion drawn by the authors. That is, IF with low-dose protein boluses was insufficient to ameliorate acute skeletal muscle wasting. Although the pattern of peak leucine concentration elicited by IF was similar to that described by Wilkinson et al,2Wilkinson D.J. Bukhari S.S.I. Phillips B.E. et al.Effects of leucine-enriched essential amino acid and whey protein bolus dosing upon skeletal muscle protein synthesis at rest and after exercise in older women.Clin Nutr. 2018; 37: 2011-2021Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar the magnitudes of increments were, however, considerably lower in the current study. With a dose of 1.5 g of leucine-enriched essential amino acid, leucine concentration increased from approximately 100 μM to a peak of 200 μM (a 100% increase) at 60 min. However, the increments of leucine concentrations reported by McNelly et al1McNelly A.S. Bear D.E. Connolly B.A. et al.Effect of intermittent or continuous feed on muscle wasting in critical illness: a phase 2 clinical trial.Chest. 2020; 158: 183-194Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar on days –1, –7, and –10 were approximately 29%, 24%, and 19%, respectively, at 60 min. Such low increments may be insufficient to stimulate short-term muscle protein synthesis (MPS). Wilkinson et al2Wilkinson D.J. Bukhari S.S.I. Phillips B.E. et al.Effects of leucine-enriched essential amino acid and whey protein bolus dosing upon skeletal muscle protein synthesis at rest and after exercise in older women.Clin Nutr. 2018; 37: 2011-2021Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar further demonstrated that higher doses of protein were needed to elicit a prolonged duration of MPS, and this may be required to significantly ameliorate acute skeletal muscle wasting. Moore et al3Moore D.R. Churchward-Venne T.A. Witard O. et al.Protein ingestion to stimulate myofibrillar protein synthesis requires greater relative protein intakes in healthy older versus younger men.J Gerontol A Biol Sci Med Sci. 2015; 70: 57-62Crossref PubMed Scopus (370) Google Scholar demonstrated that 0.24 g of protein per kilogram is required for optimal MPS in healthy young adults, and older adults require a higher amount (0.4 g/kg). From e-Table 12 in McNelly et al,1McNelly A.S. Bear D.E. Connolly B.A. et al.Effect of intermittent or continuous feed on muscle wasting in critical illness: a phase 2 clinical trial.Chest. 2020; 158: 183-194Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar we estimated that the mean weight of patients who received IF was 71 kg, and each IF bolus contained 11 g of protein. This translates to 0.15 g of protein per kilogram—a level that is considerably lower than the protein doses reported by Moore et al.3Moore D.R. Churchward-Venne T.A. Witard O. et al.Protein ingestion to stimulate myofibrillar protein synthesis requires greater relative protein intakes in healthy older versus younger men.J Gerontol A Biol Sci Med Sci. 2015; 70: 57-62Crossref PubMed Scopus (370) Google Scholar Therefore, the nil findings of McNelly et al1McNelly A.S. Bear D.E. Connolly B.A. et al.Effect of intermittent or continuous feed on muscle wasting in critical illness: a phase 2 clinical trial.Chest. 2020; 158: 183-194Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar may be attributed to insufficient protein bolus. Compounded by the fact that critically ill patients are more anabolic resistant,4Wolfe R.R. The 2017 Sir David P Cuthbertson Lecture: Amino acids and muscle protein metabolism in critical care.Clin Nutr. 2018; 37: 1093-1100Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar it is likely that higher protein boluses would be required to sufficiently ameliorate acute skeletal muscle wasting. Nevertheless, the sinusoid curves observed in Figures 4A-4C in McNelly et al1McNelly A.S. Bear D.E. Connolly B.A. et al.Effect of intermittent or continuous feed on muscle wasting in critical illness: a phase 2 clinical trial.Chest. 2020; 158: 183-194Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar hold promise for future trials to increase the dose of protein boluses, or perhaps use leucine supplementation to optimize MPS. Such studies may also clarify the current controversies surrounding the benefits/harm of providing higher protein in early critical illness.5Preiser J.C. High protein intake during the early phase of critical illness: yes or no?.Crit Care. 2018; 22: 261Crossref PubMed Scopus (17) Google Scholar Effect of Intermittent or Continuous Feed on Muscle Wasting in Critical Illness: A Phase 2 Clinical TrialCHESTVol. 158Issue 1PreviewIntermittent feeding in early critical illness is not shown to preserve muscle mass in this trial despite resulting in a greater achievement of nutritional targets than continuous feeding. However, it is feasible and safe. Full-Text PDF ResponseCHESTVol. 158Issue 6PreviewWe thank Gunst et al and Lew et al for their interest in and thoughtful comments regarding our trial of intermittent vs continuous feeding in the critically ill.1 Full-Text PDF" @default.
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• W3108379747 title "The Dose of Protein Bolus Matters" @default.
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