Context: High dose glucocorticoids (GC) cause acute protein loss by increasing protein breakdown and oxidation. Whether lower GC doses, typical of therapeutic use, induce sustained catabolism has not been studied.

Objective: To assess the effect of acute and chronic therapeutic GC doses on protein metabolism.

Design: An open longitudinal and a cross-sectional study.

Setting: A clinical research facility.

Patients and intervention: Ten healthy subjects were studied before and after a short course of prednisolone (5mg/d and 10mg/d sequentially for 7 days each). Twelve subjects with inactive polymyalgia rheumatica receiving chronic (>12 months) prednisone (mean = 5.0+0.8 mg/d) were compared to 12 age- and gender-matched normal subjects.

Main outcome measure: Whole body protein metabolism was assessed using a 3-h primed constant infusion of 1-[¹³C] leucine, from which rates of leucine appearance (leucine Ra, an index of protein breakdown), leucine oxidation (Lox, index of protein oxidation) and leucine incorporation into protein (LIP, index of protein synthesis) were estimated.

Results: Prednisolone induced an acute significant increase in Lox (p=0.008) and a fall in LIP (p=0.08), but did not affect leucine Ra. There was no significant difference between the effects of the 5mg and 10mg prednisolone doses on leucine metabolism. In subjects receiving chronic prednisone therapy, leucine Ra, Lox and LIP were not significantly different to normal subjects.

Conclusion: GCs stimulate protein oxidation after acute but not chronic administration. This time-related change suggests that GC-induced stimulation of protein oxidation does not persist but that a metabolic adaptation occurs to limit protein loss.