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Randomized Controlled Trial
. 2022 Nov 17;26(1):358.
doi: 10.1186/s13054-022-04232-5.

Effect of an enteral amino acid blend on muscle and gut functionality in critically ill patients: a proof-of-concept randomized controlled trial

Nicholas Heming  1   2   3   4 , Robert Carlier  5   6 , Helene Prigent  7   6 , Ahmed Mekki  5   6 , Camille Jousset  5   6 , Frederic Lofaso  7   6 , Xavier Ambrosi  1   8 , Rania Bounab  1 , Virginie Maxime  1 , Arnaud Mansart  2   3   4 , Pascal Crenn  6   9 , Pierre Moine  1   2   3   4 , Fabien Foltzer  10 , Bernard Cuenoud  11 , Tobias Konz  10 , John Corthesy  10 , Maurice Beaumont  10 , Mickaël Hartweg  10 , Claudia Roessle  11 , Jean-Charles Preiser  12 , Denis Breuillé  10 , Djillali Annane  13   14   15   16
Affiliations
Randomized Controlled Trial

Effect of an enteral amino acid blend on muscle and gut functionality in critically ill patients: a proof-of-concept randomized controlled trial

Nicholas Heming et al. Crit Care. .

Abstract

Background: A defining feature of prolonged critical illness is muscle wasting, leading to impaired recovery. Supplementation with a tailored blend of amino acids may bolster the innate gut defence, promote intestinal mucosa repair and limit muscle loss.

Methods: This was a monocentric, randomized, double-blind, placebo-controlled study that included patients with sepsis or acute respiratory distress syndrome. Patients received a specific combination of five amino acids or placebo mixed with enteral feeding for 21 days. Markers of renal function, gut barrier structure and functionality were collected at baseline and 1, 2, 3 and 8 weeks after randomization. Muscle structure and function were assessed through MRI measurements of the anterior quadriceps volume and by twitch airway pressure. Data were compared between groups relative to the baseline.

Results: Thirty-five critically ill patients were randomized. The amino acid blend did not impair urine output, blood creatinine levels or creatinine clearance. Plasma citrulline levels increased significantly along the treatment period in the amino acid group (difference in means [95% CI] 5.86 [1.72; 10.00] nmol/mL P = 0.007). Alanine aminotransferase and alkaline phosphatase concentrations were lower in the amino acid group than in the placebo group at one week (ratio of means 0.5 [0.29; 0.86] (P = 0.015) and 0.73 [0.57; 0.94] (P = 0.015), respectively). Twitch airway pressure and volume of the anterior quadriceps were greater in the amino acid group than in the placebo group 3 weeks after randomization (difference in means 10.6 [0.99; 20.20] cmH20 (P = 0.035) and 3.12 [0.5; 5.73] cm3/kg (P = 0.022), respectively).

Conclusions: Amino acid supplementation increased plasma citrulline levels, reduced alanine aminotransferase and alkaline phosphatase levels, and improved twitch airway pressure and anterior quadriceps volume. Trial registration ClinicalTrials.gov, NCT02968836. Registered November 21, 2016.

Keywords: Critical illness; Intensive care unit; Nutrition; Protein balance; Sepsis.

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Conflict of interest statement

Nicholas Heming, Robert Carlier, Helene Prigent, Ahmed Mekki, Camille Jousset, Frederic Lofaso, Xavier Ambrosi, Rania Bounab, Virginie Maxime, Arnaud Mansart, Pascal Crenn, Pierre Moine and Djillali Annane declare no competing interests. Fabien Foltzer: former Nestlé employee, Bernard Cuenoud: Nestlé employee, Tobias Konz: former Nestlé employee, John Corthésy: Nestlé employee, Maurice Beaumont: former Nestlé employee, Claudia Roessle: former Nestlé employee, co-author of 2 patents filed by Nestlé Research in 2021 based on the results of the current study. Mickaël Hartweg: Nestlé employee, Jean-Charles Preiser: consultancy/speakers’ fees for Danone Nutricia/Fresenius/Nestlé HS. Denis Breuillé: Nestlé employee, co-author of 2 patents filed by Nestlé Research in 2021 based on the results of the current study.

Figures

Fig. 1
Fig. 1
Indexed muscle volume of the anterior compartment of the quadriceps (cc/kg) in the amino acid and placebo groups. Anterior quadriceps volume was measured semi-automatically using isometric T1-weighted 3D images. Data are presented as the mean value of both legs. Muscle volume was indexed to the body weight. Values reported are mean changes from baseline at days 7, 14, 21 and 60, using a restricted maximum likelihood (REML)-based repeated measures approach. P < 0.05 at V4 and at V5
Fig. 2
Fig. 2
Twitch airway pressure (cm H2O) in the amino acid and placebo groups. Twitch airway pressure was measured following magnetic stimulation over the spinal processes between C5 and C7. Values reported are mean changes from baseline at days 7, 14, 21 and 60, using a restricted maximum likelihood (REML)-based repeated measures approach. P < 0.05 at V4
Fig. 3
Fig. 3
Plasma I-FABP (pg/mL) in the amino acid and placebo groups. Plasma I-FABP was assessed by ELISA. Values reported are mean changes from baseline at days 7, 14, 21 and 60, using a restricted maximum likelihood (REML)-based repeated measures approach
Fig. 4
Fig. 4
Plasma citrulline (nmol/mL) in the amino acid and placebo groups. Plasma citrulline concentration was assessed by ion exchange chromatography with spectrophotometric detection after ninhydrin derivatization. Values reported are mean changes from baseline at days 7, 14, 21 and 60, using a restricted maximum likelihood (REML)-based repeated measures approach. P < 0.05 at V4 and P < 0.01 at V5
Fig. 5
Fig. 5
Alanine aminotransferase (UI/L) in the amino acid and placebo groups. Alanine aminotransferase concentration was assessed by spectrophotometry. Values reported are mean changes from baseline at days 7, 14, 21 and 60, using a restricted maximum likelihood (REML)-based repeated measures approach. P < 0.05 at V2
Fig. 6
Fig. 6
Alkaline phosphatase (UI/L) in the amino acid and placebo groups. Alkaline phosphatase concentration was assessed by spectrophotometry. Values reported are mean changes from baseline at days 7, 14, 21 and 60, using a restricted maximum likelihood (REML)-based repeated measures approach. P < 0.02 at V2, P < 0.001 at V3, P < 0.002 at V4
Fig. 7
Fig. 7
Total bilirubin (µmol/L) in the amino acid and placebo groups. Total bilirubin concentration was assessed by spectrophotometry. Values reported are mean changes from baseline at days 7, 14, 21 and 60, using a restricted maximum likelihood (REML)-based repeated measures approach
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