Increasing protein dose does not further augment muscle protein synthesis in critical illness: A Randomized, Controlled Clinical Trial

Abstract Rationale Critical illness impairs the muscle protein synthetic response to protein administration. Whether increased protein dose can overcome this anabolic resistance is unknown. Objectives To assess the impact of a single intraduodenal bolus of 40 g protein compared to 20 g of protein in mechanically ventilated critically ill patients on the primary outcome of postprandial muscle protein synthesis rates. Methods Mechanically ventilated patients were randomized to 40 g or 20 g of whey protein isolate delivered intraduodenally over 1 h. Primed continuous intravenous L-ring-13C6-phenylalanine and L-3,5-2H2-tyrosine infusions were applied with repeated arterial blood and skeletal muscle tissue sampling over 2 h fasting and 6 h postprandial periods to assess plasma amino acid responses and rates of fasting and post-prandial muscle protein synthesis . (primary outcome). Data are mean ± SD and area under the curve (AUC), analyzed with ANCOVA adjusted for fasting rate and paired t-tests (P .05). Measurements and Main Results Twenty patients (n = 10/group: 40 g: 90% male, 49 ± 21 y and 20 g: 80% male, 51 ± 13 y) were studied. Postprandial muscle protein synthesis rates (primary outcome) did not differ between groups (40 g vs 20 g: 0.030 ± 0.012 vs 0.025 ± 0.010%·h−1; adjusted mean difference 0.007 (95% CI -0.003, 0.016) %·h−1; P = .152). Postprandial plasma leucine and tyrosine availability (AUC) were higher following 40 g vs 20 g protein (leucine: 263 ± 87 vs 194 ± 54 µmol·L−1, P = .005; tyrosine: 92 ± 24 vs 63 ± 17 µmol·L−1, P = .006). Fasting muscle protein synthesis rates did not differ between groups (40 g vs 20 g: 0.020 ± 0.012 vs 0.025 ± 0.023%·h−1; P = .558). The post-hoc uncontrolled analysis of muscle protein synthesis rates from fasting to postprandial periods increased in the 40 g group only (P = .005). Conclusion Higher enteral protein does not further augment postprandial muscle protein synthesis rates to overcome anabolic resistance during critical illness, despite increased plasma amino acid availability. Trial registration number Australia New Zealand Clinical Trials Registry Identifier: ACTRN12620000776909