Context: Alterations in dietary macronutrient intake can influence protein turnover.

Objective: To assess the influence of a low-carbohydrate/high-protein diet (LC/HP) on skeletal muscle protein synthesis and whole-body proteolysis, without the confounding influence of a negative energy balance.

Design: Nine day dietary intervention

Setting: Subjects remained in the General Clinical Research Center throughout the 9d study.

Participants: Eight young, healthy volunteers.

Intervention: Subjects ate a typical "western diet" (60% carbohydrate, 30% fat, 10% protein) for 2d, immediately followed by 7d of an isocaloric LC/HP diet (5% carbohydrate, 60% fat, 35% protein).

Main Outcome Measures: Skeletal muscle fractional synthetic rate (FSR) and whole-body proteolysis (leucine rate of appearance in plasma [Ra]) were measured after an overnight fast before, and after 2d and 7d of LC/HP. We also measured plasma concentrations of insulin, growth hormone (GH) and IGF-1.

Results: Leucine Ra was increased (P = 0.03) after 2d and 7d of LC/HP, and muscle FSR was 2 fold higher (P < 0.01) after 7d of LC/HP. Fat free mass was not altered by LC/HP. Average 24 h plasma insulin concentration was 50% lower (P < 0.001) after 2d and 7d of LC/HP, while GH secretion and total plasma IGF-1 concentrations were unchanged with LC/HP. However, plasma free IGF-1 decreased by 30% after 7d of LC/HP (P = 0.002) while muscle IGF-1 mRNA increased about 2-fold (P = 0.05).

Conclusions: Increasing dietary protein content during a 7d carbohydrate restricted diet stimulated muscle protein synthesis and whole-body proteolysis without a measurable change in fat free mass.