Positive energy balance accelerates muscle atrophy and increases erythrocyte glutathione turnover rate during 35 days 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 (ΔFM, assessed by bioelectrical impedance analysis). Results: In pooled subjects (n = 19; median ΔFM: 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 HEBAB (-3.8 ± 0.4kg and -0.32 ± 0.04 cm, respectively) than in LEBab (-2.3 ± 0.5 kg and -0.09 ± 0.04 cm, respectively) subjects. In study A (median ΔFM: 1.8 kg), bed rest-mediated increases in plasma leptin, C-reactive protein, and myeloperoxidase were greater (P < 0.04) in HEBA than in LEBA subjects. Bed rest-mediated changes of glutathione synthesis rate in eythrocytes (L-[3,3-2H2]cysteine incorporation) were greater (P = 0.03) in HEBA (from 70 ± 19 to 164 ± 29%/d) than in LEBA (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.