Clenbuterol is a popular drug used by bodybuilders and athletes that belongs to a class of compounds known as beta-agonists that bind to the beta-adrenergic receptor embedded in the cell membrane? turning on cellular signaling cascades within the fat cell that break down body fat while in the muscle cell and activating muscle growth. These functions bestow clenbuterol with the extraordinary capability to decrease body fat while supporting muscle growth.Although clenbuterol is a powerful bodybuilding compound, it also has several drawbacks. One of those drawbacks being the rapid inhibition of clenbuterol activity within the cell that swiftly shuts down its fat-burning and muscle-building activity. In addition, recent scientific evidence has shown that clenbuterol not only loses its anabolic potency rather quickly? but it may also stimulate muscle atrophy if taken for extensive periods of time, by increasing the amount of the muscle-depleting molecule myostatin within the muscle cell.
Myostatin is a member of the transforming growth factor-beta (TGF-beta) super family of growth factors where, despite being a growth factor, it actually reduces muscle growth by initiating several pathways that inhibit muscle hypertrophy while stimulating muscle atrophy. However, certain nutritional supplements have been shown to inhibit myostatin activity, which should prevent clenbuterol-stimulated muscle loss while enhancing clenbuterol-driven muscle growth. In addition, these myostatin-inhibiting compounds should also lower the amount of clenbuterol necessary for muscle growth, which would also diminish cellular inhibition of clenbuterol within the cell? further enhancing the anabolic properties of clenbuterol.
Reducing Myostatin Function Boosts Clenbuterol?s Anabolic Activity
One key investigation clearly demonstrated that inhibiting myostatin function improved clenbuterol activity. This study by Kim et al.1 showed that clenbuterol, which has previously been shown to enhance muscle size via the mTOR pathway2, works well in combination with myostatin inhibition to additively stimulate muscle growth and strength. The researchers took normal mice and myostatin-deficient mice and fed them clenbuterol. After two weeks, muscle biopsies revealed an additive effect on mTOR activation in the myostatin-deficient mice that were also fed clenbuterol. These myostatin-deficient mice that were fed clenbuterol had an increase in muscle mass of ~25 percent. The result of this investigation demonstrates that inhibiting myostatin clearly enhances clenbuterol function.
Clenbuterol Amplifies the Level of Muscle-depleting Myostatin
Considering the previously mentioned study by Kim et al.1 which showed that clenbuterol stimulates greater muscle growth when combined with myostatin inhibition,a recent study by Abo et al.3 investigated whether this inhibitory function of myostatin on clenbuterol was induced by clenbuterol consumption. In this study, they analyzed the level and activity of myostatin in the muscle of rats that were given clenbuterol for 21 days straight. Muscle hypertrophy was induced from day 3 to 14, which corresponded to increased levels of the muscle-building growth factor IGF1. In addition, the study also showed increased levels and activity of myostatin after consuming clenbuterol for 21 days. These results show that myostatin function is induced by clenbuterol where it functions as a negative regulator in the later stages of clenbuterol use, whereas IGF1 works as a positive regulator in the earlier stages.
Creatine and Vitamin D Decrease Myostatin and Enhance Clenbuterol
Certain nutritional supplements are known to inhibit myostatin. Therefore, consuming them should negate myostatin?s hold on muscle growth directly induced by clenbuterol. Creatine is a well-characterized compound that has been unmistakably shown to enhance muscle size and strength. In addition to creatine?s obvious function as a primary energy storage molecule used to regenerate muscle ATP, thus prolonging muscle function, creatine has also been shown to stimulate muscle growth.4 More recently, however, a study by Saremi et al.5 demonstrated that creatine consumption causes a decrease in myostatin levels in muscle cells, leading to significant muscle growth. In this study, two groups of men performed resistance training with or without creatine for a total of eight weeks. Both groups showed decreased levels of myostatin, but the group that performed resistance training and consumed creatine had a considerably larger decrease in myostatin levels along with greater gains in muscle mass and strength? clearly demonstrating the ability of creatine to reduce myostatin levels, improving muscle growth and strength.
Another potent myostatin inhibitor is vitamin D. As shown in a recent study by Garcia et al.6, vitamin D exposure decreased the amount of myostatin found in isolated muscle cells, generating greater muscle growth. In addition to the decrease in myostatin, this study also showed that vitamin D triggers an increase in the powerful inhibitor of myostatin known as follistatin, which increases muscle mass by inhibiting myostatin.7 Ultimately, this study indicates that the decrease in myostatin level and activity caused by vitamin D significantly increased muscle fiber size.
Essential Amino Acids Drive Muscle Growth by Reducing Myostatin
While essential amino acids (EAAs) have been shown to potently activate mTOR-stimulated muscle protein synthesis, leading to greater muscle size8,9, a more recent study by Drummond et al.10 demonstrated that EAAs also have the uniquely powerful ability to decrease genetic expression of myostatin in muscle cells. EAAs decrease myostatin levels by stimulating the production of a class of molecules known as micro-RNA that have the ability to strongly decrease the expression level of specific genes. The unique finding in this study was that several micro-RNA molecules were produced in human skeletal muscle following the ingestion of 10 grams of EAAs, which subsequently decreased myostatin expression by approximately 50 percent. Although further work is needed to elucidate the precise role that micro-RNA has in the regulation of myostatin and muscle mass following EAA consumption, this investigation represents a completely novel way to decrease myostatin levels for enhanced muscle growth.
In summary, although clenbuterol has the extraordinary capability to stimulate fat loss while supporting muscle growth, clenbuterol directly increases myostatin levels? which may drive substantial muscle loss. On the other hand, myostatin is such an extremely responsive target that even a minor reduction of clenbuterol-increased myostatin levels should restore clenbuterol activity, boosting notable muscle growth and fat loss. As a result, clenbuterol?s ability to increase myostatin function should be mitigated by simultaneously consuming clenbuterol with the right nutritional supplements that inhibit myostatin and restore clenbuterol function that only cuts fat and not muscle growth.