Protein Ingestion before Sleep Increases Overnight Muscle Protein Synthesis Rates in Healthy Older Men: A Randomized Controlled Trial.

Background: The loss of skeletal muscle mass with aging has been attributed to the blunted anabolic response to protein intake. Presleep protein ingestion has been suggested as an effective strategy to compensate for such anabolic resistance.Objective: We assessed the efficacy of presleep protein ingestion on dietary protein digestion and absorption kinetics and overnight muscle protein synthesis rates in older men.Methods: In a randomized, double-blind, parallel design, 48 older men (mean ± SEM age: 72 ± 1 y) ingested 40 g casein (PRO40), 20 g casein (PRO20), 20 g casein plus 1.5 g leucine (PRO20+LEU), or a placebo before sleep. Ingestion of intrinsically l-[1-13C]-phenylalanine- and l-[1-13C]-leucine-labeled protein was combined with intravenous l-[ring-2H5]-phenylalanine and l-[1-13C]-leucine infusions during sleep. Muscle and blood samples were collected throughout overnight sleep.Results: Exogenous phenylalanine appearance rates increased after protein ingestion, but to a greater extent in PRO40 than in PRO20 and PRO20+LEU (P < 0.05). Overnight myofibrillar protein synthesis rates (based on l-[ring-2H5]-phenylalanine) were 0.033% ± 0.002%/h, 0.037% ± 0.003%/h, 0.039% ± 0.002%/h, and 0.044% ± 0.003%/h in placebo, PRO20, PRO20+LEU, and PRO40, respectively, and were higher in PRO40 than in placebo (P = 0.02). Observations were similar based on l-[1-13C]-leucine tracer (placebo: 0.047% ± 0.004%/h and PRO40: 0.058% ± 0.003%/h, P = 0.08). More protein-derived amino acids (l-[1-13C]-phenylalanine) were incorporated into myofibrillar protein in PRO40 than in PRO20 (0.033 ± 0.002 and 0.019 ± 0.002 MPE, respectively, P < 0.001) and tended to be higher than in PRO20+LEU (0.025 ± 0.002 MPE, P = 0.06).Conclusions: Protein ingested before sleep is properly digested and absorbed throughout the night, providing precursors for myofibrillar protein synthesis during sleep in healthy older men. Ingestion of 40 g protein before sleep increases myofibrillar protein synthesis rates during overnight sleep. These findings provide the scientific basis for a novel nutritional strategy to support muscle mass preservation in aging and disease. This trial was registered at www.trialregister.nl as NTR3885.

Physical Activity Performed in the Evening Increases the Overnight Muscle Protein Synthetic Response to Presleep Protein Ingestion in Older Men.

BACKGROUND: The age-related decline in skeletal muscle mass is partly attributed to anabolic resistance to food intake. Dietary protein ingestion before sleep could be used as a nutritional strategy to compensate for anabolic resistance. OBJECTIVE: The present study assessed whether physical activity performed in the evening can augment the overnight muscle protein synthetic response to presleep protein ingestion in older men. METHODS: In a parallel group design, 23 healthy older men (mean ± SEM age: 71 ± 1 y) were randomly assigned to ingest 40 g protein intrinsically labeled with l-[1-(13)C]-phenylalanine and l-[1-(13)C]-leucine before going to sleep with (PRO+EX) or without (PRO) performing physical activity earlier in the evening. Overnight protein digestion and absorption kinetics and myofibrillar protein synthesis rates were assessed by combining primed, continuous infusions of l-[ring-(2)H5]-phenylalanine, l-[1-(13)C]-leucine, and l-[ring-(2)H2]-tyrosine with the ingestion of intrinsically labeled casein protein. Muscle and blood samples were collected throughout overnight sleep. RESULTS: Protein ingested before sleep was normally digested and absorbed, with 54% ± 2% of the protein-derived amino acids appearing in the circulation throughout overnight sleep. Overnight myofibrillar protein synthesis rates were 31% (0.058% ± 0.002%/h compared with 0.044% ± 0.003%/h; P < 0.01; based on l-[ring-(2)H5]-phenylalanine) and 27% (0.074% ± 0.004%/h compared with 0.058% ± 0.003%/h; P < 0.01; based on l-[1-(13)C]-leucine) higher in the PRO+EX than in the PRO treatment. More dietary protein-derived amino acids were incorporated into de novo myofibrillar protein during overnight sleep in PRO+EX than in PRO treatment (0.042 ± 0.002 compared with 0.033 ± 0.002 mole percent excess; P < 0.05). CONCLUSIONS: Physical activity performed in the evening augments the overnight muscle protein synthetic response to presleep protein ingestion and allows more of the ingested protein-derived amino acids to be used for de novo muscle protein synthesis during overnight sleep in older men. This trial was registered at Nederlands Trial Register as NTR3885.