Anabolic response to amino acid supplementation in critical illness

Abstract

Background: Critically ill patients suffer from protein catabolism with losses of skeletal muscle and whole-body proteins associated with morbidity and mortality. Catabolism is difficult to overcome, but nutritional supplementation with enteral protein or parenteral amino acids may limit protein losses. It is unknown which dose, mode, and timing of feeding is optimal for critically ill patients.

Aim: The aim of this project was to evaluate a technique of quantifying the response of protein turnover to feeding, then apply it to study effects of protein or amino acid supplementation in critical illness. A main question was whether exogenous protein/amino acid is utilized for improved protein balance, or else consumed in catabolic pathways.

Methods: In study 1, a previously characterized cohort of viscerally obese, insulin-resistant women was studied. Postprandial muscle and whole-body protein turnover were quantified by stable-isotope labeled phenylalanine tracers. In study 2, the whole-body technique was adapted to investigate the effects of early enteral feeding in critically ill patients. In study 3, the response of critically ill patients to a three-hour course of intravenous supplemental amino acids was studied. In study 4, the time course of uptake of stable-isotope-labeled phenylalanine from the intestine into arterial blood was studied in healthy subjects and critically ill patients during continuous enteral feeding.

Results: In study 1, the technique was found workable to quantify postprandial protein metabolism, and it was found that viscerally obese women are resistant to postprandial stimulation of anabolism. In study 2, it was found in critically ill patients that enteral feeding of a small amount of protein yields a detectable gain in protein balance and no increase in amino acid oxidation. In study 3, an improvement in whole-body protein balance after three hours of intravenous amino acid supplementation was found in critically ill patients. In study 4, the uptake of dietary phenylalanine from continuous enteral feeding was found to reach a tentative steady state, but with high intra- and interindividual variability.

Conclusion: Exogenous amino acids from enteral or intravenous nutrition improve protein balance in healthy subjects and critically ill patients, and are not predominantly consumed in catabolic pathways.