What markers track muscle protein synthesis?
A research-catalogue summary of the markers and models used to track muscle protein synthesis, including HMB, IGF-I, whey and casein, and the mTOR-centred signalling work behind them.
What markers track muscle protein synthesis?
Muscle protein synthesis (MPS) is tracked in the research literature through a set of surrogate markers rather than a single readout. The most commonly reported are intracellular anabolic signalling through the mechanistic target of rapamycin (mTOR) pathway, transcriptomic changes in skeletal muscle biopsy material, and downstream tissue outcomes such as lean body mass and muscle size. Circulating hormones such as insulin-like growth factor I (IGF-I) are also used as markers in some doping-control and sports research contexts [1].
The pathway at the centre of most of this work is mTOR signalling, which is reported as the mechanistic node through which amino acid and metabolite availability is translated into protein synthesis and, in some models, reduced protein breakdown [2][6].
Research Studies
HMB and the human skeletal muscle transcriptome
Beta-hydroxy beta-methylbutyrate (HMB) is an endogenous metabolite of the essential amino acid leucine. In a study of young males (n = 14), total RNA was extracted from m. vastus lateralis muscle biopsies before and approximately 2.5 hours after oral consumption of approximately 3 g HMB. The work examined mechanistic effects on the muscle transcriptome, noting that HMB has anabolic properties in skeletal muscle and acutely stimulates muscle protein synthesis while attenuating muscle protein breakdown [2].
HMB and protein kinase activity in exercise models
A registered study assessed the influence of HMB free acid supplementation at 90 mg/kg of fat-free body mass per day for 21 days on protein kinase activity and selected hormone levels, with subsequent improvements in muscle protein synthesis, lean body mass content and aerobic capacity as outcomes [7].
HMB and mTOR signalling in cirrhosis-associated sarcopenia
Loss of skeletal muscle mass, or sarcopenia, is described as the most common and potentially reversible complication in cirrhosis. Investigators hypothesised that reduced skeletal muscle mass in cirrhosis is due to a myostatin-mediated impairment of mTOR signalling, resulting in reduced protein synthesis and increased autophagy, and proposed HMB-enriched amino acids as an intervention [6].
HMB and post-operative muscle mass in female athletes
A randomised clinical trial evaluated musculoskeletal outcomes of quadriceps and hamstring muscle size and function following orthopaedic knee surgery involving anterior cruciate ligament repair or reconstruction. The study compared standard of care plus calcium-beta-hydroxy-beta-methylbutyrate (caHMB) against placebo in female athletes [5].
HMB and pulmonary rehabilitation in lung transplant candidates
A registered trial evaluated hydroxymethylbutyrate supplementation in lung transplant candidates receiving pulmonary rehabilitation, with nutritional status optimisation during the waiting period as the stated rationale [3].
Whey and casein and acute anabolic signalling after strength training
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 hypothesised that native whey would give 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 as doping-control markers
Human chorionic gonadotropin (hCG) and IGF-I are both included in the WADA list of banned molecules. 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. A technical note described the development of a UHPLC-MS/MS method for the analysis of hCG and IGF-I from dried blood spots, with dry matrix microsampling proposed to improve compound stability and simplify sample collection and pre-analytic phases [1].
Metformin and muscle outcomes in elderly type 2 diabetes
Sarcopenia is an age-related geriatric syndrome characterised by reductions in muscle mass, muscle strength and/or physical function. A registered study examined metformin in elderly patients with type 2 diabetes in relation to muscle strength, muscle mass and physical function, noting elevated sarcopenia prevalence among patients with diabetes [4].
Comparison of marker classes across models
| Marker class | Example readout | Model or population | Source |
|---|---|---|---|
| Transcriptomic | Muscle RNA from m. vastus lateralis biopsies | Young males (n = 14) | [2] |
| Signalling kinase activity | Protein kinase activity, selected hormones | HMB free acid, 21-day protocol | [7] |
| Pathway signalling | Myostatin-mediated mTOR impairment | Cirrhosis-associated sarcopenia | [6] |
| Tissue size and function | Quadriceps and hamstring size and function | Female athletes post-ACL surgery | [5] |
| Circulating hormone | IGF-I, hCG from dried blood spots | Doping-control analytical method | [1] |
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Sources
- [1] Technical note: Development of a UHPLC-MS/MS method for the analysis of hCG and IGF-I from dried blood spots
- [2] The Influence of Acute Beta-Hydroxy Beta-Methylbutyrate (HMB) Ingestion on the Human Skeletal Muscle Transcriptome
- [3] Evaluation of Hydroxymethylbutyrate Supplementation in Lung Transplant Candidates Receiving Pulmonary Rehabilitation
- [4] Metformin in Elderly Patients With Type 2 Diabetes and Muscle Strength, Muscle Mass, and Physical Function
- [5] Influence of β-hydroxy β-methyl Butyrate (HMB) Supplementation on Post-operative Muscle Mass and Function in Female Athletes
- [6] HMB Enriched Amino Acids to Reverse Muscle Loss in Cirrhosis
- [7] The Impact of Exercise / Stress Stimuli on HMB Supplementation Efficacy
- [8] Anabolic Effects of Whey and Casein After Strength Training in Young and Elderly