New Research Suggests These Compounds May
Decrease Muscle-Limiting Myostatin Levels


What is myostatin? Myostatin is a myokine (a substance released from muscle) that negatively regulates muscle mass by blunting protein synthesis (and cell differentiation) and stimulating catabolism---essentially halting muscle growth and promoting muscle loss. When we weight train, myostatin levels go down, which promotes increased protein synthesis and muscle building. In contrast, long bouts of inactivity lead to upregulation of myostatin, resulting in muscle loss.

Since the discovery of the myostatin gene in 1997, scientists have toiled to understand its regulation and have searched for safe and effective ways to silence myostatin’s catabolic influences. Several studies have shown that knocking out the gene for myostatin in mice produces super muscular rodents, and it has been shown that the ultra-muscular Belgian Blue bull has a myostatin gene mutation. There are even ridiculous rumors that several Mr. Olympia bodybuilders lack “the myostatin gene."

How can we manipulate myostatin levels? Ever since the identification of the myostatin factor, researchers and manufacturers have undertaken research aimed at creating compounds that might decrease myostatin levels. Indeed, a few products have emerged as a result of this research, to mixed results. Interestingly, however, we may be seeing a classic case of “losing sight of the forest for the trees,” as several possible myostatin inhibitors may very well be right under our noses. In this article we hone in on three common supplements that have been linked to modulation of myostatin in clinical tests.

1) Creatine Monohydrate

Creatine is synthesized by the body from arginine, methionine, and glycine and is stored in skeletal muscle. During exercise, it plays a fundamental role in energy production by forming the ATP needed for muscle contractions.

When taken after exercise, creatine monohydrate can replenish and significantly boost muscle creatine stores. Having extra creatine around after training not only provides energy substrates for future exercise bouts, but also promotes greater protein synthesis in recovery via physical and hormonal mechanisms. First, it increases the amount of water taken up by muscle cells---which swells the muscle and signals for increased repair (it also makes your muscles look bigger).  Second, it increases the release of the anabolic hormone, insulin-like growth factor 1 (IGF-1).

Recently, the effects of 8 weeks of weight training combined with creatine supplementation on strength, lean mass, serum levels of myostatin and growth and differentiation factor-associated serum protein-1 (GASP-1) were evaluated in a clinical study. Twenty-seven males were assigned to either a control group, weight training + placebo group, or weight training + creatine group. Subjects exercised 3 days per week at 60-70% 1-RM with six exercises per workout (i.e., bench press, lat pull downs, biceps curl, leg press, knee extension, and hamstring curls). Creatine or placebo was loaded for the first week at 0.3g/kg/day and maintained thereafter at 0.05g/kg/day.
 
Blood was sampled for myostatin and GASP-1, and strength and body composition were measured at weeks 0, 4, and 8. The exercise + placebo condition actually decreased myostatin levels and increased GASP-1 at week 4 and 8. However, those who took creatine and trained had twice the reduction in myostatin at weeks 4 and 8 compared to those training with the placebo! In addition, training with creatine supplementation increased upper and lower body strength and lean body mass better than resistance training with placebo.

2) Leucine Paired with Creatine Monohydrate

Research has proven leucine and its metabolites to be unequivocal anabolic activators and muscle builders, as they are primarily involved in protein synthesis. In fact, a study published in The American Journal of Clinical Nutrition in 2011 showed that taking leucine-enriched amino-acid supplements during exercise enhances protein synthesis by more than 30%!  

Leucine makes up only 5% to 10% of proteins and blood leucine levels are known to decline by about 30% during strength training and 11% to 33% during fat burning cardio sessions (i.e., aerobic exercise). As such, research has shown that leucine requirements are much higher in athletes. It is reported that supplementation with leucine at 50 mg/kg bodyweight per day prevents the decrease in blood leucine levels during intense strength training. Thus, for bodybuilders, leucine supplementation makes sense as a means to boost or enrich the leucine complement of your current protein intake.

A recent study published in the Journal of the International Society of Sports Nutrition suggests that leucine, HMB (a metabolite of leucine), and creatine monohydrate can effectively prevent myostatin-induced muscle atrophy (breakdown). Using an in vitro approach, the scientists investigated whether leucine, HMB, and/or creatine monohydrate could reverse the muscle-wasting effects of myostatin application in myoblasts (immature muscle cells). The authors postulated that leucine (and HMB) and creatine reversed the atrophy produced by myostatin through altering genetic mechanisms driving myotube differentiation (the process by which myotubes convert into mature muscle cells).   

3) Glutamine

Glutamine is the most abundant amino acid found in skeletal muscle and is depleted during and after heavy physical stress. Thus, years of research have shown that supplementing glutamine before and after training leads to greater protein synthesis and decreased catabolism.

Experimental evidence indicates that the muscle sparing and anabolic effects of glutamine supplementation are (at least partially) due to its ability to inhibit myostatin. In a study published in Amino Acids, researchers from the University of Torino (in Italy) showed that when muscle cells were exposed to TNFα (to induce catabolism) and supplemented with glutamine, it completely reversed the hyperactivity of myostatin (and halted catabolism). This finding is supported by earlier work, published in Metabolism, which reported that myostatin-induced catabolism (stimulated by corticosteroid treatment) was attenuated with glutamine supplementation.  

Supplement Stacking Suggestions
Based on This Compelling Science

Clearly, there’s still plenty of research left to be done on the effects of creatine monohydrate, leucine, and glutamine on myostatin production. And indeed, that research is ongoing. At the same time, stacking leucine, creatine, and glutamine is already well-indicated for support of muscle growth and recovery, and if a degree of myostatin modulation comes along as part of the bargain, so much the better! To this end, the following regimen is recommended:

30 minutes PRE-WORKOUT:
Take 5 g leucine, glutamine, and creatine with a protein shake. As a protein source, a superior-quality premium protein like NytroWhey Ultra Elite fits the bill perfectly. NytroWhey Ultra Elite is a cutting-edge complex of protein technologies including a super-pure whey isolate, ultra-rapid-action whey hydrolysate, and (most significantly for our purposes here) a revolutionary patent-pending leucine-peptide carrier technology that enables leucine to remain soluble and stable, thus increasing bioavailability. Mix NytroWhey Ultra Elite with 5 g of a premium-grade 100% pure and free-form source of glutamine such as ProSource-brand Glutamine Powder. Then add 5 g of creatine monohydrate and you have the perfect pre-workout anabolism-triggering cocktail that may just do double duty on the myostatin front as well. Oh, and yes, ProSource’s Creatine Monohydrate, 100% sourced with Creapure™ creatine, far and away the world’s best, IS an unrivaled value and your best creatine choice.

Immediately POST-WORKOUT:
Take 5 g leucine, glutamine, and creatine with a protein shake. Here, frankly, you could just go the NytroWhey Ultra Elite route again, but there’s another formula ideally suited for your post-workout mass-building purposes, in the form of BioQuest’s MyoZene. MyoZene offers a convenient “one stop solution” to post-workout supplementation that may address myostatin modulation as well. MyoZene is a post-workout supplement, clinically validated for spurring significant strength increases in a product-specific four-week clinical study, that contains the same ground-breaking leucine-peptide technology found in NytroWhey Ultra Elite, as well as clinically indicated doses of glutamine and Creapure™ creatine monohydrate. Serious bodybuilders have sworn by MyoZene and its ultra-anabolic power for years now, and we may just now be discovering another reason for that ecstatic support!

Myostatin inhibition is a subject of great importance to bodybuilders everywhere, and you can count on ProSource to keep you abreast of the latest developments in this area of sports nutrition science. In the meantime, supplement smartly with leucine, creatine monohydrate, and glutamine. And consider the distinct possibility that sometimes the solution to complex physiological puzzles can sometimes be a lot closer to hand than we think!


Read more about ProSource Creatine Monohydrate here.

Read more about NytroWhey Ultra Elite here.

Read more about BioQuest MyoZene here.


Scientific References

Saremi A, Gharakhanloo R, Sharghi S, Gharaati MR, Larijani B, Omidfar K. Effects of oral creatine and resistance training on serum myostatin and GASP-1.Mol Cell Endocrinol. 2010 Apr 12;317(1-2):25-30.

Pasiakos SM, McClung HL, McClung JP, Margolis LM, Andersen NE, Cloutier GJ, Pikosky MA, Rood JC, Fielding RA, Young AJ. Leucine-enriched essential amino acid supplementation during moderate steady state exercise enhances postexercise muscle protein synthesis. Am J Clin Nutr. 2011 Sep;94(3):809-18.

Bonetto A, Penna F, Minero VG, Reffo P, Costamagna D, Bonelli G, Baccino FM, Costelli P. Glutamine prevents myostatin hyperexpression and protein hypercatabolism induced in C2C12 myotubes by tumor necrosis factor-α. Amino Acids. 2011 Feb;40(2):585-94.

Salehian B1, Mahabadi V, Bilas J, Taylor WE, Ma K. The effect of glutamine on prevention of glucocorticoid-induced skeletal muscle atrophy is associated with myostatin suppression. Metabolism. 2006 Sep;55(9):1239-47.

Mobley CB, Fox CD, Ferguson BS, Amin RH, Dalbo VJ, Baier S, Rathmacher JA, Wilson JM, Roberts MD. L-leucine, beta-hydroxy-beta-methylbutyric acid (HMB) and creatine monohydrate prevent myostatin-induced Akirin-1/Mighty mRNA down-regulation and myotube atrophy. J Int Soc Sports Nutr. 2014 Aug 13;11:38.



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