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Hedi Raizer

Journal 6 min read

Common Misconceptions About Muscle Protein Synthesis: What the Research Literature Actually Shows

A research-supply review of muscle protein synthesis misconceptions, covering HMB, IGF-I, whey and casein, and the mTOR pathway as reported in laboratory and clinical study records. For research use only.

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What muscle protein synthesis is, in formal terms

Muscle protein synthesis (MPS) is the metabolic process by which amino acids are incorporated into new contractile and structural proteins within skeletal muscle. In the research literature it is also referred to as skeletal muscle protein synthesis, muscle protein accretion, or, in the context of net turnover, muscle protein balance. It is a physiological process rather than a discrete compound, and it therefore has no sequence, molecular formula, or molecular weight of its own; the identifiers that appear in the evidence base belong to the individual compounds studied as modulators of the process, such as beta-hydroxy beta-methylbutyrate (HMB), an endogenous metabolite of the essential amino acid leucine [2], and insulin-like growth factor I (IGF-I), a hormone included on the WADA list of banned molecules [1].

The mechanistic work in this area centres on the mechanistic target of rapamycin (mTOR) signalling pathway, which is described in the evidence base as the pathway through which impaired signalling is hypothesised to reduce protein synthesis and increase autophagy in conditions of muscle loss [6].

Research Studies

HMB and the human skeletal muscle transcriptome in young males

HMB is described in the evidence base as an anabolic agent in skeletal muscle that acutely stimulates muscle protein synthesis and attenuates muscle protein breakdown [2]. A study of the acute effects of HMB ingestion on the human skeletal muscle transcriptome extracted total RNA from m. vastus lateralis muscle biopsies of young males (n = 14) before and approximately 2.5 hours after oral consumption of approximately 3 g HMB [2]. The stated rationale for the work was that, while the role of supplemental HMB on muscle protein turnover is established, mechanistic effects on the muscle transcriptome had not been examined [2].

HMB and protein kinase activity in an exercise-stress model

A registered study assessed the influence of HMB free acid supplementation at 90 mg/kg of fat free body mass per day, supplemented for 21 days, on protein kinase activity and selected hormone levels, and on subsequent improvements in muscle protein synthesis, lean body mass content, and aerobic capacity [7]. This record frames HMB as a variable acting alongside an exercise or stress stimulus rather than in isolation [7].

HMB and post-operative muscle mass and function in female athletes

A randomised clinical trial record describes evaluation of musculoskeletal outcomes of quadriceps and hamstring muscle size and function following orthopaedic knee surgery involving anterior cruciate ligament repair or reconstruction, comparing current standard of care plus supplementation of calcium-beta-hydroxy-beta-methylbutyrate (caHMB) against placebo in female athletes [5]. The record states that caHMB has been shown to impart effects in this context [5].

HMB-enriched amino acids and muscle loss in cirrhosis

In cirrhosis, loss of skeletal muscle mass, or sarcopenia, is described as the most common and potentially reversible complication, increasing morbidity and mortality before, during, and after liver transplantation [6]. The investigators hypothesise that the mechanism of reduced skeletal muscle mass in cirrhosis is due to a myostatin-mediated impairment of mTOR signalling, resulting in reduced protein synthesis and increased autophagy [6]. The record notes that no proven treatments exist for the prevention or reversal of sarcopenia in cirrhosis, primarily because the responsible mechanisms are unknown [6].

HMB and nutritional status in lung transplant candidates

A registered study evaluates hydroxymethylbutyrate supplementation in lung transplant candidates receiving pulmonary rehabilitation [3]. The record states that optimising nutritional status during the waiting period before transplantation is important for vital functions such as exercise capacity, for early mobilisation after transplantation, for shortening hospitalisation, and for supporting survival [3].

Whey and casein and anabolic signalling after strength training

A study record describes investigation of 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 [8]. The investigators hypothesised 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 analytical detection in dried blood spots

A technical note reports development of a UHPLC-MS/MS method for the analysis of hCG and IGF-I from dried blood spots [1]. The record states that male athletes may use pharmaceutical preparations of hCG to stimulate testosterone production before competition and IGF-I to stimulate muscle protein synthesis, promote glycogen storage, and improve lipolysis [1]. Dry matrix microsampling and dried blood spots are described as promising strategies for doping control, with potential improvements in compound stability, simplification of sample collection and pre-analytic phases, and facilitation of automation [1].

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

A registered study examines metformin in elderly patients with type 2 diabetes in relation to muscle strength, muscle mass, and physical function, framed as a question of positive or negative correlation [4]. The record cites the 2019 report from the Asian Working Group for Sarcopenia, which gave a sarcopenia prevalence among elderly Asians of 5.5% to 25.7%, with males exhibiting higher rates (5.1% to 21.0%) than females (4.1% to 16.3%) [4]. Among patients with diabetes, sarcopenia incidence was reported as significantly elevated, with a prevalence of 14.8% reported in Chinese patients [4].

Comparison of study models and reported populations

Compound or interventionModel or populationReported focus
HMBYoung males, n = 14, m. vastus lateralis biopsiesMuscle transcriptome ~2.5 h after ~3 g oral HMB [2]
HMB free acidRegistered study, 21-day supplementation at 90 mg/kg FFM/dayProtein kinase activity, hormone levels, MPS, lean body mass, aerobic capacity [7]
caHMBFemale athletes after ACL repair or reconstructionQuadriceps and hamstring size and function versus placebo [5]
HMB-enriched amino acidsCirrhosisMyostatin-mediated impaired mTOR signalling, protein synthesis, autophagy [6]
HydroxymethylbutyrateLung transplant candidates in pulmonary rehabilitationNutritional status, exercise capacity, survival [3]
Native whey, WPC-80, milkYoung and elderly after strength trainingAcute anabolic effects and intracellular anabolic signalling [8]
IGF-IDried blood spot analytical methodDetection of a WADA-banned hormone [1]
MetforminElderly patients with type 2 diabetesMuscle strength, mass, physical function; sarcopenia prevalence [4]

If you are reading this for personal health reasons

The materials described here are sold for laboratory research use only, and we do not provide dosing or medical guidance of any kind. Nothing in this article is a recommendation for personal use, and no outcome is promised or implied. Anyone considering a compound for themselves should speak to a licensed clinician.

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