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How does muscle protein synthesis work?

Muscle protein synthesis (MPS) is the process by which skeletal muscle builds new protein. This page covers the mTOR-centred mechanism and the research models used to study it, including HMB, whey, casein, IGF-I and hCG.

What muscle protein synthesis is

Muscle protein synthesis (MPS) is the process by which skeletal muscle tissue assembles new protein from amino acid precursors. It is the anabolic half of muscle protein turnover, the other half being muscle protein breakdown. In the research literature the term is used interchangeably with 'muscle protein synthesis' and 'MPS'; the process is not a single molecule but a cellular state, so it has no sequence, formula or molecular weight of its own. What the evidence block describes are the agents and models used to study it: beta-hydroxy beta-methylbutyrate (HMB), an endogenous metabolite of the essential amino acid leucine [2]; insulin-like growth factor I (IGF-I), a hormone on the WADA list of banned molecules [1]; and the milk-derived proteins native whey, whey protein concentrate 80 (WPC-80) and milk [8].

The pathway the work centres on is mechanistic target of rapamycin (mTOR) signalling, which in cirrhosis research is described as myostatin-mediated and impaired, resulting in reduced protein synthesis and increased autophagy [6].

Research Studies

HMB and the human skeletal muscle transcriptome

HMB has anabolic properties in skeletal muscle: acutely stimulating muscle protein synthesis and attenuating muscle protein breakdown. While the role of supplemental HMB on muscle protein turnover is established, mechanistic effects on the muscle transcriptome had not been examined. Total RNA was extracted from m. vastus lateralis muscle biopsies of young males (n = 14) before and approximately 2.5 h after oral consumption of approximately 3 g HMB [2].

HMB and protein kinase activity in exercise and stress models

A study assessed the influence of HMB free acid supplementation (90 mg/kg of fat free body mass/day) supplemented for 21 days on protein kinases activity and selected hormones levels, and subsequent improvements in muscle protein synthesis, lean body mass content and aerobic capacity [7].

HMB and muscle loss in cirrhosis

Loss of skeletal muscle mass, or sarcopenia, is the most common and potentially reversible complication in cirrhosis and increases morbidity and mortality before, during and after liver transplantation. No proven treatments exist for the prevention or reversal of sarcopenia in cirrhosis, primarily because the mechanisms responsible are unknown. Investigators hypothesize that the mechanism of reduced skeletal muscle mass in cirrhosis is due to a myostatin mediated impaired mTOR signalling resulting in reduced protein synthesis and increased autophagy [6].

HMB and post-operative muscle mass in female athletes

A randomized clinical trial is proposed to observe muscular outcomes following standard of care plus supplementation of calcium-beta-hydroxy-beta-methylbutyrate (caHMB) or placebo. The project evaluates quadriceps and hamstring muscle size and function following orthopedic knee surgery involving anterior cruciate ligament (ACL) repair or reconstruction. CaHMB has been shown to improve musculoskeletal outcomes in this setting [5].

HMB and lung transplant candidates receiving pulmonary rehabilitation

Lung transplantation (LTx) is an accepted treatment option for patients with end-stage lung disease who do not respond to non-transplant treatments. It is important to optimize the nutritional status of patients during the waiting period before transplantation, to positively improve vital functions such as exercise capacity, to get up as soon as possible after transplantation, to shorten the hospitalization process and to support survival. Pulmonary rehabilitation (PR) aims to prevent further progression of respiratory disease and improve outcomes [3].

Whey and casein after strength training in young and elderly

A study investigated the acute anabolic effects of native whey, whey protein concentrate 80 (WPC-80) and milk after a bout of strength training in young and elderly participants. The investigators hypothesized that native whey would give a greater stimulation of muscle protein synthesis and intracellular anabolic signalling than WPC-80, and that WPC-80 would give a stronger stimulus than milk [8].

IGF-I and hCG in doping-control analysis

Two of the most used hormones in sport, included in the WADA list of banned molecules, are human chorionic gonadotropin (hCG) and insulin-like growth factor (IGF-I). Male athletes may use pharmaceutical preparations of hCG to stimulate the production of testosterone before competition and IGF-I to stimulate muscle protein synthesis, promote glycogen storage, and improve lipolysis. Dry matrix microsampling and dried blood spots (DBS) are promising strategies to improve current doping control activities, as they can lead to a significant improvement in compound stability, the simplification of sample collection and pre-analytic phases, and the facilitation of their automation and a reduction in cost [1].

Metformin and muscle strength, mass and physical function in elderly type 2 diabetes

With the accelerating aging process in China, sarcopenia has drawn increasing attention. Sarcopenia is an age-related geriatric syndrome characterized by reductions in muscle mass, muscle strength, and/or physical function. According to the 2019 report from the Asian Working Group for Sarcopenia (AWGS), sarcopenia prevalence among elderly Asians ranged from 5.5% to 25.7%, with males exhibiting higher rates (5.1% to 21.0%) than females (4.1% to 16.3%). Particularly among patients with diabetes, sarcopenia incidence was significantly elevated, with a prevalence of 14.8% reported in Chinese diabetes patients [4].

If you are reading this for personal health reasons

The compounds discussed on this page are sold for laboratory research use only. We do not provide dosing or medical guidance, and nothing here is a recommendation for human use. Anyone considering a compound for themselves should speak to a licensed clinician.

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