The Effect of Enteral Glycine on Plasma Glycine and Muscle Loss in Critical Illness

Résumé fourni par la source

Abstract RATIONALE: Glycine attenuates muscle loss in pre-clinical models of muscle wasting. Aim: To evaluate the absorption of enteral glycine and impact of glycine supplementation on muscle loss in critically ill adults. METHODS: Single-centre, placebo-controlled, blinded, randomized clinical trial. Patients anticipated to be mechanically ventilated for ≥48 hours were randomized to receive a test meal supplemented with 0.067g/kg or 0.133g/kg glycine (low and high-dose intervention groups) or placebo (control group), mixed with 100mL of standard enteral formula (1.25 kcal/mL, protein 20%). The test meal was delivered over 30 minutes to measure glycine absorption. Participants received ongoing daily enteral supplements (low- [0.2g/kg/day], high- [0.4g/kg/day] dose glycine or placebo) for 7 days or until extubation. Day 0 plasma samples were collected prior to the test meal, and every 30 minutes until T=240 minutes. Quadriceps muscle thickness was measured with ultrasound on Days 0, 3 and 7. Needle biopsies of the vastus lateralis muscle were collected at baseline and Day 7. The primary outcome was glycine absorption measured using gas chromatography-mass spectrometry and analysed as area under the curve 0-240 minutes. Secondary outcomes included muscle glycine concentration, markers of muscle inflammation or wasting, myofibre cross-sectional diameter, quadriceps thickness, physical function 1 week post-ICU discharge and length of stay. Secondary analyses were adjusted for corresponding baseline values. RESULTS: Twenty-nine patients were enrolled and randomized to placebo (n=10), low-dose (n=9) or high-dose glycine (n=10). Median age was 52 [IQR: 37-61] years, 75% male, APACHE III 67 [55-89] and weight 93 [74-102] kg. All patients survived until Day 7. Patients received 12.4 (3.8-12.8) g and 18.9 (10.1-28.4) g of glycine per day in the low and high-dose intervention groups.With supplementation there was a dose-dependent, statistically significant increase in plasma glycine (Figure 1A) and muscle glycine concentrations (Figure 1B). Point estimates favoured an attenuated loss of quadriceps thickness in patients receiving high-dose glycine supplementation compared to placebo at Day 7 (mean difference from mixed model: 0.13; 95% CI -0.07 to 0.33) (Figure 1C). Length of stay was shorter in the glycine groups when compared to placebo (low-dose vs high-dose glycine vs placebo: ICU 11.2 (9.5-12.2) vs 11.5 (6.6-17.4) vs 15.6 (12.7-22.1) days; hospital 22.5 (16.2-27.8) vs 23.4 (17.4-29.1) vs 31.6 (17.4-44.2) days). There were no differences in myofibre diameter (Figure 1D) or other secondary outcomes. CONCLUSION: Glycine supplementation results in a dose-dependent rise in plasma and muscle glycine, may attenuate ultrasound-derived quadriceps loss and warrants evaluation in larger trials.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.