What does the research say about muscle protein synthesis?
A research-supply overview of muscle protein synthesis as studied with HMB, IGF-I, whey and casein, metformin and related compounds in human, animal and in vitro models.
Muscle protein synthesis (MPS) is the process by which amino acids are incorporated into skeletal muscle proteins. In the research literature it is also referred to as muscle protein turnover, skeletal muscle anabolism, or myofibrillar protein synthesis. The process is regulated by the mechanistic target of rapamycin (mTOR) pathway, and it is this pathway that most of the studies below use as their readout.
MPS is not a compound but a biological process. The compounds discussed here are research reagents and study interventions used to probe that process: beta-hydroxy beta-methylbutyrate (HMB), insulin-like growth factor I (IGF-I), whey and casein proteins, and metformin. Where a finding comes from an animal model or an in vitro system, that is stated explicitly.
Research Studies
HMB and the human skeletal muscle transcriptome
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 about 3 g HMB. The authors note that HMB has anabolic properties in skeletal muscle, acutely stimulating muscle protein synthesis and attenuating muscle protein breakdown, and 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 model
A registered study assessed the influence of HMB free acid supplementation (90 mg/kg of fat-free body mass per day) 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]. The study design links an exercise or stress stimulus to the proposed mechanism.
HMB and mTOR signalling in cirrhosis
In cirrhosis, loss of skeletal muscle mass (sarcopenia) is the most common and potentially reversible complication. Investigators hypothesize 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]. This is a hypothesis under test in a clinical population, not an established mechanism.
HMB and post-operative muscle mass in female athletes
A randomized clinical trial is evaluating musculoskeletal outcomes of quadriceps and hamstring muscle size and function following orthopedic knee surgery involving anterior cruciate ligament (ACL) repair or reconstruction. The trial observes muscular outcomes following standard of care plus supplementation of calcium-beta-hydroxy-beta-methylbutyrate (caHMB) or placebo [5].
HMB and pulmonary rehabilitation in lung transplant candidates
A registered study evaluates hydroxymethylbutyrate supplementation in lung transplant candidates receiving pulmonary rehabilitation. The rationale is to optimize nutritional status during the waiting period before transplantation and to support exercise capacity and recovery [3].
IGF-I and muscle protein synthesis in doping control research
IGF-I is included in the WADA list of banned molecules. Male athletes may use pharmaceutical preparations of IGF-I to stimulate muscle protein synthesis, promote glycogen storage, and improve lipolysis. A technical note describes the development of a UHPLC-MS/MS method for the analysis of hCG and IGF-I from dried blood spots, a strategy intended to improve compound stability and simplify sample collection in doping control [1].
Whey and casein after strength training in young and elderly
A study investigates 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 hypothesize that native whey will give a greater stimulation of muscle protein synthesis and intracellular anabolic signalling than WPC-80, and that WPC-80 will give a stronger stimulus than milk [8].
Metformin and muscle strength, mass and physical function in elderly patients with type 2 diabetes
A registered study examines whether metformin correlates positively or negatively with muscle strength, muscle mass and physical function in elderly patients with type 2 diabetes. The background notes that 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%), and that among patients with diabetes sarcopenia incidence was significantly elevated, with a prevalence of 14.8% reported in Chinese data [4].
Comparison of study models and compounds
| Compound or intervention | Model or population | Reported or hypothesized mechanism |
|---|---|---|
| HMB | Young males (n = 14), m. vastus lateralis biopsies | Acute stimulation of muscle protein synthesis; transcriptome effects [2] |
| HMB free acid | Exercise or stress stimulus study | Protein kinase activity; muscle protein synthesis, lean body mass, aerobic capacity [7] |
| HMB | Cirrhosis (clinical hypothesis) | Myostatin-mediated impaired mTOR signalling [6] |
| caHMB | Female athletes after ACL surgery | Post-operative muscle size and function [5] |
| Hydroxymethylbutyrate | Lung transplant candidates | Nutritional status and exercise capacity [3] |
| IGF-I | Doping control (dried blood spots) | Stimulation of muscle protein synthesis, glycogen storage, lipolysis [1] |
| Whey, WPC-80, milk | Young and elderly after strength training | Acute anabolic effects and intracellular anabolic signalling [8] |
| Metformin | Elderly with type 2 diabetes | Correlation with muscle strength, mass, physical function [4] |
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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: A preliminary study.
- [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: Positive or Negative Correlation?
- [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.