Creatine, Leucine, & HMB Are Myostatin Inhibitors

The muscle cells formed muscle fibers, but the presence of myostatin inhibited the process. Leucine, HMB and above all creatine reduced the inhibitory effect. And this effect is largely bound up with the activity of the Mighty gene.

Leucine, HMB and creatine probably all boost muscle growth because they reduce the functioning of myostatin, the protein that causes muscles to atrophy. Molecular scientists at Auburn University in the US write about it in the Journal of the International Society of Sports Nutrition. The researchers did in-vitro studies on the effects of leucine, HMB and creatine on muscle cells.

Myostatin Inhibitors

Muscle cells slow down their own growth by producing the protein myostatin. By more or less deactivating that protein you can build up more muscle mass and strength, so scientists all over the world are searching for myostatin blockers.

Most of the research has been done by pharmacologists, but some studies have also been published on the effect of lifestyle factors and supplements on myostatin synthesis. Five years ago, for example, Iranian researchers reported that they had been able to reduce myostatin production in strength athletes by giving them a creatine supplement.

Study

The researchers exposed young C2C12 muscle cells to myostatin [MSTN] and to three well-studied components of bodybuilding supplements: creatine [CrM], leucine and HMB.

Results

As a result of the myostatin, the muscle cells produced less MyoD, but the presence of leucine, HMB and creatine corrected this. MyoD is an anabolic signal molecule that is involved in muscle fibre growth. It enables stem cells to attach themselves to muscle fibres.

Leucine and HMB, but above all creatine, stimulated activity of the Mighty gene in the muscle cells. This gene sabotages the functioning of myostatin. Another name for Mighty is Akirin-1.

The muscle cells formed muscle fibers, but the presence of myostatin inhibited the process. Leucine, HMB and above all creatine reduced the inhibitory effect. And this effect is largely bound up with the activity of the Mighty gene.

Mighty

Because they wanted to know for sure whether the Mighty gene is crucial to muscle growth the researchers did another experiment. This time they deactivated the Mighty gene using s-RNA. The figures below show that in the muscle cells where this happened [shRNA Akirin-1] fewer muscle fibers were indeed formed than in muscle cells in which the Mighty gene was still active [shRNA scrambled].

Conclusion

"We demonstrated that leucine, HMB, and creatine monohydrate reverse myostatin-induced atrophy in myotubes", the researchers summarize. "This potentially results from the independent action of each ingredient modulating Akirin-1/Mighty mRNA expression. Furthermore, our findings suggest that, in spite of myostatin treatments, creatine monohydrate treatment up-regulates Akirin-1/Mighty mRNA which leads to a hypertrophic effect clearly independent of muscle protein synthesis."

"Future in vivo studies should continue to examine how leucine, HMB, and/or creatine monohydrate independently or synergistically affect Akirin-1/Mighty gene expression. More importantly, while Akirin-1/Mighty gene expression is needed for the maintenance of myofiber size as reported herein, further research is needed in order to examine how Akirin-1/Mighty gene expression mechanistically relates to skeletal muscle hypertrophy in vivo."

So the researchers wonder whether creatine, leucine and HMB can reinforce each other's myostatin inhibitory effect. This idea becomes more plausible if you take into account the evidence that leucine and HMB probably stimulate muscle growth via different mechanisms.

Source:
J Int Soc Sports Nutr. 2014 Aug 13;11:38.