The effect of enteral glycine on plasma glycine and muscle structure, size, and function in the critically ill: A randomized controlled trial

Abstract

Background

Critically ill patients frequently experience severe muscle loss with subsequent physical impairment. In pre-clinical models of muscle wasting, administration of the amino acid glycine attenuates muscle loss.

Aims

To evaluate the plasma availability of enteral glycine and the impact of glycine supplementation on muscle loss in critical illness.

Methods

Parallel group, blinded, randomized clinical trial. Mechanically ventilated patients were randomized to receive low- or high-dose glycine (0.2 or 0.4 g/kg/day) or placebo, in addition to usual care, for a maximum of 7 days. On day 1, plasma samples were obtained at regular intervals for 240 min to measure glycine concentrations. Quadriceps muscle thickness was measured with ultrasound at baseline, days 3 and 7. Needle biopsies of the vastus lateralis muscle were obtained at baseline and end of intervention. The primary outcome was plasma glycine availability (plasma glycine area under curve over 240 min, AUC₂₄₀). Secondary outcomes included muscle glycine concentration, myofiber diameter, quadriceps muscle thickness, physical function and length of stay.

Results

Twenty-nine patients were randomized (placebo n = 10, low-dose glycine n = 9, high-dose glycine n = 10). Patients received a median (interquartile range) of 16.2 (4.6–16.4) g and 29.6 (24.8–32.4) g glycine per day in the low- and high-dose intervention groups. There was a dose-dependent increase in plasma glycine availability (Mean difference AUC₂₄₀ high-dose glycine vs placebo: 759.40 μmol/L.min; 95 % CI 219.27, 1299.54, p = 0.008) and muscle glycine concentration (Mean difference high-dose glycine vs placebo: 0.16 nmol/mg muscle wet mass; 95 % CI 0.08, 0.23, p = 0.001). Point estimates favoured attenuated loss of quadriceps muscle thickness in patients receiving high-dose glycine (Mean difference high-dose glycine vs placebo: 0.11 cm; 95 % CI: −0.10, 0.31, p = 0.299). However, glycine supplementation had no effect on myofiber diameter. Patients who received glycine had shorter ICU and hospital admissions.

Conclusion

In critically ill patients, glycine supplementation increases plasma and muscle glycine concentrations and the effect of glycine on muscle loss warrants further evaluation in larger studies.

Trial registration

This trial was prospectively registered with the Australian and New Zealand Clinical Trials Registry (www.anzctr.org.au) ANZCTR ACTRN12618000409279.