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Muscle disuse leads to muscle atrophy that has been attributed to declines in basal and postprandial muscle protein synthesis (MPS) rates. Leucine regulates MPS and may attenuate disuse-induced declines in MPS rates and muscle mass. The purpose of this study was to evaluate the capacity of leucine supplementation to attenuate disuse-induced declines in MPS rates and muscle mass in young and older adults. In a randomized, double-blind, parallel-group design, 24 young (23±4y) and 24 older (69±4y) recreationally active adults (equal sex distribution) underwent 3 days of unilateral knee immobilization (leg casting) and received a leucine (LEU) or energy-matched carbohydrate (PLA) supplement (5g, 3×daily). Pre- and post-immobilization, quadriceps muscle cross-sectional area (CSA) was assessed in the immobilized (IM) and non-immobilized (NO-IM) leg by computed tomography. MPS rates were assessed in both legs during immobilization via 2 H 2 O coupled with saliva, blood, and muscle biopsy sampling. In young and older adults, MPS rates were ∼15 and ∼23% lower in the IM versus NO-IM leg (1.28±0.29 versus 1.50±0.26 and 1.10±0.16 versus 1.46±0.28 %•day -1 , respectively; leg: both P <0.001), with no differences between LEU versus PLA treatments (treatment: P =0.932 and P =0.742, respectively). CSA decreased by ∼1.2 and ∼1.1% in the IM leg in young and older adults (from 7162±1148 to 7076±1129 mm 2 and from 5813±1092 to 5750±1096 mm 2 , respectively; leg × time interaction: both P <0.001), with no differences between LEU versus PLA (treatment: P =0.374 and P =0.998). IM leg MPS rates were lower in older versus young adults (difference: -0.18 (95% CI: -0.31, -0.04) %•day -1 ; P =0.013). No differences were observed in the absolute (mm 2 ) or relative (%) decline in CSA between young and older adults (both P >0.05). Leucine supplementation does not attenuate the decline in daily MPS rates or muscle mass during short-term limb immobilization in young or older adults. This trial was prospectively registered at Netherlands Trial Register: https://onderzoekmetmensen.nl/en/trial/45771 as ID: NL-OMON45771
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Churchward-Venne et al. (2026) studied this question.
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