Increasing protein dose does not further augment muscle protein synthesis in critical illness: a randomized, controlled clinical trial

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 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 postprandial 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 to 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.