Effect of High-Protein Diets on Integrated Myofibrillar Protein Synthesis before Anterior Cruciate Ligament Reconstruction: A Randomized Controlled Pilot Study

Abstract

Increasing dietary protein intake during periods of muscle disuse may mitigate the resulting decline in muscle protein synthesis (MPS). The purpose of this randomized pilot study was to determine the effect of increased protein intake during periods of disuse before anterior cruciate ligament (ACL) reconstruction on myofibrillar protein synthesis (MyoPS), and proteolytic and myogenic gene expression. Six healthy, young males (30 ± 9 y) were randomized to consume a high-quality, optimal protein diet (OP; 1.9 g·kg − 1·d − 1) or adequate protein diet (AP; 1.2 g·kg − 1·d − 1) for two weeks before ACL reconstruction. Muscle biopsies collected during surgery were used to measure integrated MyoPS during the intervention (via daily deuterium oxide ingestion) and gene expression at the time of surgery. MyoPS tended to be higher, with a large effect size in OP compared to AP (0.71 ± 0.1 and 0.54 ± 0.1%·d − 1; p = 0.076; g = 1.56). Markers of proteolysis and myogenesis were not different between groups (p > 0.05); however, participants with greater MyoPS exhibited lower levels of MuRF1 gene expression compared to those with lower MyoPS (r = −0.82, p = 0.047). The data from this pilot study reveal a potential stimulatory effect of increased daily protein intake on MyoPS during injury-mediated disuse conditions that warrants further investigation.

Depressed Protein Synthesis and Anabolic Signaling Potentiate ACL Tear–Resultant Quadriceps Atrophy

“…26 This disconnect could be unique to mouse skeletal muscle, as previous work from our group and others has shown strong associations between phosphorylation of AKT-mTORC1 signaling proteins and rates of protein synthesis in human muscle. 14,24,36 In addition, our current data show agreement between E3 ubiquitin ligase transcript and protein expression data in human skeletal muscle. Our current data offer intriguing insight into comparative differences between human and mouse muscle in the regulation of protein metabolism.…”

“…A recent pilot study showed that provision of a protein supplement did not rescue deficits in quadriceps protein synthesis after ACL injury. 24 It appears that the addition of protein alone is insufficient to reverse the intrinsic deficits in translation signaling that we find in the ACL-injured quadriceps. Adjunctive therapies to stimulate muscle protein synthesis after injury—including pharmacology, 59 electrical stimulation, 61 mesenchymal/pluripotent stem cell–derived treatment, 13,31,68 and/or medical nutrition therapy 2 —may better preserve quadriceps mass and function after reconstruction as compared with traditional rehabilitation alone.…”

“…16 It is unknown how the effects of feeding would modify the effect of ACLT that we observed in the current study, and future research should ascertain whether ACL injury mitigates nutrient-induced stimulation of muscle protein anabolism. 24 While anabolic deficits in mouse tissue are robust after ACLT, future work would benefit from functional analyses. Assessment of quadriceps strength or gait alteration would add functional depth, linking protein metabolic perturbations to weakness.…”

“…11,25 Importantly, mitigation of atrogene expression-muscle ring finger 1 (MuRF1), tripartite motif containing 63 (TRIM63) and atrogin-1, muscle atrophy F-box (MAFbx), and F-box protein 32 (FBXO32)-was unable to offset quadriceps atrophy, 11 suggesting that protein catabolism is not the dominant mechanism causing ACL injury-induced muscle atrophy. Limited and underpowered data 24 from human studies have impeded translation of preclinical findings as well as the development of targeted therapies to attenuate atrophy.…”

The Role of Perioperative Nutritional Status and Supplementation in Orthopaedic Surgery

“…Similarly, nutritional supplementation and high-protein diets after anterior cruciate ligament reconstruction have shown increased muscle anabolism and reduction in muscle atrophy, as well as improved pain, clinical outcomes, and graft maturation 146-148 . From the evidence currently available, nutritional intervention can benefit tendinous and ligamentous injury management, but further research is required to identify the optimal combinations of nutrients and magnitude of benefit 10,149 .…”