Positive energy balance is associated with accelerated muscle atrophy and increased erythrocyte glutathione turnover during 5 wk of bed rest

Background: Physical inactivity is often associated with positive energy balance and fat gain. Objective: We aimed to assess whether energy intake in excess of requirement activates systemic inflammation and antioxidant defenses and accelerates muscle atrophy induced by inactivity. Design: Nineteen healthy male volunteers were studied before and at the end of 5 wk of bed rest. Subjects were allowed to spontaneously adapt to decreased energy requirement (study A, n = 10) or were provided with an activity-matched diet (study B, n = 9). Groups with higher (HEB) or lower (LEB) energy balance were identified according to median values of inactivity-induced changes in fat mass (Delta FM, assessed by bioelectrical impedance analysis). Results: In pooled subjects (n = 19; median Delta FM: 1.4 kg), bed rest-mediated decreases in fat-free mass (bioelectrical impedance analysis) and vastus lateralis thickness (ultrasound imaging) were significantly greater (P < 0.03) in HEB(AB) (-3.8 +/- 0.4 kg and -0.32 +/- 0.04 cm, respectively) than in LEB(AB) (-2.3 +/- 0.5 kg and -0.09 +/- 0.04 cm, respectively) subjects. In study A(median Delta FM: 1.8 kg), bed rest-mediated increases in plasma leptin, C-reactive protein, and myeloperoxidase were greater (P < 0.04) in HEB A than in LEB A subjects. Bed rest-mediated changes of glutathione synthesis rate in eythrocytes (L-[3,3-(2)H(2)] cysteine incorporation) were greater (P = 0.03) in HEB A (from 70 +/- 19 to 164 +/- 29%/ d) than in LEB(A) (from 103 +/- 23 to 84 +/- 27%/d) subjects. Conclusions: Positive energy balance during inactivity is associated with greater muscle atrophy and with activation of systemic inflammation and of antioxidant defenses. Optimizing caloric intake may be a useful strategy for mitigating muscle loss during period of chronic inactivity.