A systematic review to assess the impact of amino acids or their derivatives on skeletal muscle wasting in critically ill patients

Background: It is plausible that supplementation with specific amino acids or metabolites could attenuate skeletal muscle wasting during critical illness. The aim of this systematic review was to explore if amino acids or their derivatives impact skeletal muscle wastage in critically ill adults. Methods: Four databases were systematically searched to identify randomised control trials which delivered enteral supplemental amino acids, or their metabolites compared with placebo, standard care or no intervention, to critically ill patients and reported outcomes of skeletal muscle mass, plasma amino acids, nitrogen balance, or muscle strength. Two authors independently completed screening, data extraction, and risk of bias assessment using the Cochrane Risk of Bias 2 Tool. A meta-analysis was planned but heterogeneity in the type of intervention used and outcome assessment precluded this. Therefore, data were synthesised using vote counting. Results: Thirty randomised control trials, comprising 1976 patients were included. The most frequently studied interventional amino acid or metabolite was glutamine (n = 12 trials), a combination (n = 9), arginine (n = 6), (3-hydroxy (3-methylbutyrate (HMB) (n = 2) or ornithine (n = 1). Six trials (including 284 participants) measured skeletal muscle following supplementation, four of which used HMB alone or in combination as the intervention. Of these, one trial observed an attenuation of muscle wasting with a combination of amino acids, one observed an exacerbation of muscle wasting with HMB, three trials observed no impact on muscle wasting with HMB or a combination of amino acids and one trial reported no information. Conclusion: Six trials have investigated the effect of enteral amino acid or amino acid metabolite supplementation on muscle mass in critically ill. Heterogeneity of interventions, outcome assessments and direction of effects limits the certainty regarding the effect of supplemental amino acids, or their metabolites, on skeletal muscle wasting during critical illness. The trial protocol is registered on PROSPERO (CRD42021275989). (c) 2024 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).