What is muscle protein synthesis?
Muscle protein synthesis (MPS) is the cellular process by which skeletal muscle builds new protein from amino acids. This page explains the pathway, the research models used to study it, and what the evidence does and do
What is muscle protein synthesis?
Muscle protein synthesis (MPS) is the metabolic process by which skeletal muscle tissue assembles new protein from amino acids. It is the anabolic half of muscle protein turnover, the continuous cycle in which muscle protein is simultaneously built and broken down. In the research literature the term is used interchangeably with "skeletal muscle protein synthesis" and, in nutritional-intervention contexts, "muscle protein accretion" when net gain is being described. MPS is not a compound and has no sequence, formula or molecular weight; it is a biological process measured indirectly, most often by isotope tracer incorporation into muscle biopsy samples.
The work described in the evidence below centres on the mechanistic target of rapamycin (mTOR) signalling pathway, which is the principal intracellular regulator of muscle protein synthesis in the models studied.
Research Studies
HMB and acute muscle protein synthesis in young males
Beta-hydroxy beta-methylbutyrate (HMB) is an endogenous metabolite of the essential amino acid leucine. In a human study, 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 roughly 3 g HMB. The authors state that HMB has anabolic properties in skeletal muscle, acutely stimulating muscle protein synthesis and attenuating muscle protein breakdown, and that its role in muscle protein turnover is established while mechanistic effects on the muscle transcriptome had not previously been examined [2].
HMB and protein kinase activity in trained populations
A registered study assessed the influence of HMB free acid supplementation (90 mg/kg of fat-free body mass per day) given for 21 days on protein kinase activity and selected hormone levels, and subsequent improvements in muscle protein synthesis, lean body mass content and aerobic capacity [7]. This is a study protocol; results are not reported in the evidence block.
HMB and muscle mass after orthopaedic knee surgery in female athletes
A randomized clinical trial evaluated musculoskeletal outcomes of quadriceps and hamstring muscle size and function following orthopaedic knee surgery involving anterior cruciate ligament (ACL) repair or reconstruction. The intervention compared standard of care plus calcium-β-hydroxy-β-methylbutyrate (caHMB) against placebo in female athletes [5].
HMB-enriched amino acids and sarcopenia in cirrhosis
Loss of skeletal muscle mass, or sarcopenia, is described as the most common and potentially reversible complication in cirrhosis, increasing morbidity and mortality before, during and after liver transplantation. The investigators hypothesize that the mechanism of reduced skeletal muscle mass in cirrhosis is myostatin-mediated impaired mTOR signalling, resulting in reduced protein synthesis and increased autophagy [6]. This is a mechanistic hypothesis under test, not an established finding.
HMB and nutritional status in lung transplant candidates
A registered study evaluates hydroxymethylbutyrate supplementation in lung transplant candidates receiving pulmonary rehabilitation. The rationale given is that optimizing nutritional status during the waiting period may improve vital functions such as exercise capacity and support recovery after transplantation [3].
Whey, casein and 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 hypothesized that native whey would produce greater stimulation of muscle protein synthesis and intracellular anabolic signalling than WPC-80, and that WPC-80 would produce a stronger stimulus than milk [8].
IGF-I and muscle protein synthesis in doping-control research
A technical note on a UHPLC-MS/MS method for analysing hCG and IGF-I from dried blood spots states that male athletes may use pharmaceutical preparations of IGF-I to stimulate muscle protein synthesis, promote glycogen storage and improve lipolysis. Both hCG and IGF-I are included in the WADA list of banned molecules [1]. This describes the rationale for analytical method development, not a therapeutic finding.
Metformin, muscle strength and sarcopenia in 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. The background cites 2019 Asian Working Group for Sarcopenia figures: sarcopenia prevalence among elderly Asians ranged from 5.5% to 25.7%, with males (5.1% to 21.0%) higher than females (4.1% to 16.3%), and a prevalence of 14.8% reported in Chinese patients with diabetes [4].
Comparison of research models
| Model / population | Intervention or exposure | Reported or hypothesised MPS-related outcome |
|---|---|---|
| Young males (n = 14), m. vastus lateralis biopsies | ~3 g oral HMB | Acute stimulation of muscle protein synthesis; transcriptome examined at ~2.5 h [2] |
| Trained participants | HMB free acid, 90 mg/kg FFM/day, 21 days | Protein kinase activity, hormone levels, MPS, lean body mass, aerobic capacity [7] |
| Female athletes post-ACL surgery | caHMB vs placebo plus standard of care | Quadriceps and hamstring muscle size and function [5] |
| Cirrhosis with sarcopenia | HMB-enriched amino acids | Hypothesised myostatin-mediated impaired mTOR signalling [6] |
| Young and elderly | Native whey, WPC-80, or milk after strength training | Acute MPS and intracellular anabolic signalling [8] |
If you are reading this for personal health reasons
The materials described on this page are supplied for laboratory research use only. We do not provide dosing information, medical guidance, or recommendations for personal use. Anyone considering a compound for themselves should speak to a licensed clinician.
Sources
- [1] Technical note: Development of a UHPLC-MS/MS method for the analysis of hCG and IGF-I from dried blood spots: A preliminary study. https://pubmed.ncbi.nlm.nih.gov/42385550/
- [2] The Influence of Acute Beta-Hydroxy Beta-Methylbutyrate (HMB) Ingestion on the Human Skeletal Muscle Transcriptome. https://europepmc.org/article/PMC/PMC12899265
- [3] Evaluation of Hydroxymethylbutyrate Supplementation in Lung Transplant Candidates Receiving Pulmonary Rehabilitation. https://clinicaltrials.gov/study/NCT07660991
- [4] Metformin in Elderly Patients With Type 2 Diabetes and Muscle Strength, Muscle Mass, and Physical Function: Positive or Negative Correlation? https://clinicaltrials.gov/study/NCT07788378
- [5] Influence of β-hydroxy β-methyl Butyrate (HMB) Supplementation on Post-operative Muscle Mass and Function in Female Athletes. https://clinicaltrials.gov/study/NCT05869812
- [6] HMB Enriched Amino Acids to Reverse Muscle Loss in Cirrhosis. https://clinicaltrials.gov/study/NCT05166499
- [7] The Impact of Exercise / Stress Stimuli on HMB Supplementation Efficacy. https://clinicaltrials.gov/study/NCT05444959
- [8] Anabolic Effects of Whey and Casein After Strength Training in Young and Elderly. https://clinicaltrials.gov/study/NCT02968888