Myostatin, also known as growth differentiation factor 8 (GDF-8), is a protein found in humans and animals. This protein acts as a natural regulator, primarily limiting the growth of skeletal muscles. Its function is to prevent muscles from becoming excessively large, thereby maintaining a balanced muscle mass within the body. Myostatin is produced and released by muscle cells, making it a significant factor in muscle development and size.
Lifestyle Strategies for Lowering Myostatin
Engaging in specific lifestyle practices, particularly exercise and nutrition, can influence myostatin levels. Resistance training, which involves working muscles against an opposing force, has been shown to temporarily decrease myostatin expression. Lifting heavy weights and training to muscular failure can particularly stimulate this reduction, contributing to increased muscle growth.
Adequate caloric intake is also important for supporting muscle growth and influencing the myostatin signaling pathway. Consuming sufficient protein, around 1.5 grams per kilogram of body weight per day, is recommended to support muscle protein synthesis. Myostatin levels in both muscle and plasma have been observed to decrease with aerobic exercise training, suggesting a broader metabolic influence.
Supplements and Investigational Drugs
Certain compounds and pharmaceutical agents have been explored for their potential to influence myostatin.
Creatine, a widely used supplement, has demonstrated myostatin inhibitory effects in preclinical studies. It promotes intracellular water retention in muscle cells, increasing their volume and potentially enhancing the uptake of other muscle-building compounds.
Epicatechin, a natural flavonoid found in foods like dark chocolate, inhibits myostatin by increasing levels of follistatin. Follistatin is a protein that binds to myostatin, neutralizing its muscle-limiting actions. This interaction allows for greater potential for muscle growth and strength.
In pharmaceutical research, investigational drugs like Stamulumab (Myo-29) and Domagrozumab (PF-06252616) have been studied for conditions such as muscular dystrophy. These are monoclonal antibodies designed to block myostatin’s activity. Stamulumab, an early myostatin inhibitor, failed to show significant improvements in muscle strength in trials, likely due to a high clearance rate.
Domagrozumab also failed to meet its primary efficacy endpoint in Phase 2 trials for Duchenne muscular dystrophy, leading to its termination, despite increasing muscle volume in animal studies. These drugs are not available for general public use for bodybuilding purposes.
Risks of Suppressing Myostatin
Suppressing myostatin can lead to negative health consequences. One concern is the possibility of weaker tendons and ligaments. These connective tissues may not strengthen at the same rate as the rapidly growing muscles, increasing the risk of injury, such as tendon ruptures.
The long-term effects of myostatin inhibition on other bodily tissues, particularly cardiac muscle, are not understood. There is concern about inflammation or other adverse impacts on the heart. Additionally, disrupting the body’s natural metabolic processes could occur.
Myostatin also plays a role in bone metabolism, and its inhibition has been linked to increased bone mineral density and regeneration in some animal models, but also to bone weakness in others, depending on the specific inhibitor. Some myostatin inhibitors may also affect other related proteins in the transforming growth factor-beta (TGF-β) family, which could lead to unintended side effects like vascular issues.
The Role of Genetics in Myostatin Levels
Genetic factors play a role in an individual’s natural myostatin levels. Some individuals and animals possess genetic mutations that result in significantly reduced or absent myostatin, leading to naturally enhanced muscle mass.
Belgian Blue cattle are a well-known example, exhibiting a “double-muscled” phenotype due to a specific myostatin gene mutation. Similarly, “bully” whippets have a two-base-pair deletion in their myostatin gene, resulting in an inactive myostatin protein and a notably muscular physique.
In humans, rare cases of myostatin-related muscle hypertrophy have been documented, where a mutation in the MSTN gene leads to increased muscle mass and strength from a young age due to the production of little or no functional myostatin. These instances highlight that myostatin deficiency dramatically increases musculature, arising from natural genetic variations rather than external interventions.