Calorie restriction accelerates the catabolism of lean body mass during 2 wk of bed rest

Background: Muscle inactivity and low energy intake commonly occur in persons with acute or chronic disease, in astronauts during space flight, and during aging. Objective: We used a crossover design to investigate the effects of the interactions of inactivity and calorie restriction on whole-body composition and protein kinetic regulation in 9 healthy volunteers. Design: Lean body mass (LBM) was measured by using dual-energy X-ray absorptionmetry before and at the end of 14-d periods of bed rest (B) and controlled ambulation (A) in patients receiving eucaloric (E) or hypocaloric (H) (approximate to 80% of total energy expenditure) diets. Whole-body leucine kinetics were determined at the end of the 4 study periods by using a standard stable-isotope technique in the postabsorptive state and during a 3-h infusion of a 0.13 g center dot kg LBM-1 center dot h(-1) amino acid mixture. Results: In the postabsorptive state, we found a significant (P = 0.04) bed rest x hypocaloric diet interaction for the rate of leucine oxidation, an index of net protein catabolism (A+E: 0.23 +/- 0.01; B + E: 25 +/- 0.01; A + H: 0.23 +/- 0.01; B + H: 0.28 +/- 0.01 mu mol center dot min(-1) center dot kg LBM-1). Bed rest significantly (P < 0.01) decreased amino acid-mediated stimulation of nonoxidative leucine disappearance, an index of protein synthesis (A + E: 35 +/- 2%; B + E: 30 +/- 2%; A + H: 41 +/- 3%; B + H: 32 +/- 2%). B + H decreased LBM by 1.10 +/- 0.1 kg, which is significantly (P < 0.01) greater than the decrease seen with A + E, A + H, or B + E. Conclusion: Calorie restriction enhanced the catabolic response to inactivity by combining greater protein catabolism in the postabsorptive state with an impaired postprandial anabolic utilization of free amino acids.