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Muscle & Performance

Athletes and bodybuilders are always looking for new ways to enhance their performance. After all, a shaved millisecond or an extra kilo of muscle could mean the difference between coming first and second and between glory and defeat. There are three main ways in which to enhance performance:

  • Nutrition and Supplementation
  • Drug therapy
  • Gene therapy

Whilst we don't advocate drug use, the first two avenues for performance enhancement have been around for a long time and while research is still ongoing, there is already a considerable knowledge and practical base for the efficacy of those two avenues in their capability to enhance performance. On the other hand however, gene therapy and manipulation of genes is still in its infancy, but there is no doubt that this is definitely the future of performance enhancement. While drugs have the capability to affect genes as well, generally they are meant to target specific proteins and other signalling molecules rather than the genes producing them. Indeed, many drug therapies for performance enhancement are also still within its infancy due to the long term safety prospects. One of the most exciting and most interesting developments in the world of gene research and muscles has been the 1997 discovery of the gene encoding the protein myostatin.

What is Myostatin?

Myostatin is a protein that prevents muscle growth to ensure that there is not an overgrowth of muscle tissues. It does so by two known mechanisms; inhibition of muscle differentiation and also inhibition of ‘Akt’ kinase induced protein synthesis. Without making to too hard to understand, muscles contain satellite cells which are usually dormant cells within the muscle. When muscle cells die or are injured by activities such as weight lifting, these satellite cells awaken and move in and start the process of repair or regeneration by first dividing into myoblasts (immature muscle cells) which are then differentiated (specialised) into skeletal myocytes (skeletal muscle cells). Myostatin will inhibit this differentiation part, thereby reducing the amount of mature muscle cells that are rebuilt. Myostatin also inhibits an enzyme known as ‘Akt kinase’, which is responsible for initiating protein synthesis among other roles. A combination of both these effects by myostatin will lead to a block in muscle growth and size. The ability to stop this protein from working then should theoretically have some serious prospects in terms of muscle and strength enhancement.

Encoding Myostatin

Before gene research techniques were advanced, farmers around the world were already playing around with genes, albeit indirectly. Selective breeding or breeding different plants and animals with desirable qualities has been around for centuries. For example, the modern day western carrot was never naturally orange. They were originally violet in colour, but through selective breeding, the orange carrot came into existence. Similarly, in the 1950s a breed of cattle known as the Belgian Blue was developed after several years of breeding of different species of extremely muscular cattle. The resulting cattle breed contained 40% more muscle than average cattle breeds and were said to be ‘double muscled’ due to their pronounced muscle mass. Genetic studies found that these cattle had mutations in the gene that encodes for myostatin, effectively causing the muscle cells to multiply. Similarly the researchers who discovered the gene encoding myostatin found that mice without this gene were twice as large and muscular as normal mice. Further tests on humans were able to show that people with mutations in both genes were considerably more muscular and had more strength. Even people with mutations in one gene had increased muscle bulk.

Supplement Companies & Myostatin

It is of no surprise then that supplement companies began to see the potential of myostatin blockers as a way to help athletes, bodybuilders and other consumers achieve greater muscle size and number and thereby their strength potential. A research article appeared in a Bulgarian journal in 20031 that was able to show that a brown seaweed (Cystoseira Canariensis) was able to block myostatin in vitro (in the lab). While no human trials were performed, this major detail did not deter one supplement company who brought out the first ‘myostatin blocker’ supplement containing the brown seaweed previously mentioned. However these supplements were proving ineffective in improving strength or muscle size gains as shown by a journal article published in 20042. The journal was able to show that the supplement itself interfered with another protein in the body known as FLRG (follistatin related gene protein) which normally inhibits myostatin. Essentially the supplement worked against itself by causing decreased levels of FLRG.

Myostatin - New Research

So far, there is no known natural nutrient that is able to successfully block myostatin. However, around the time the supposed ‘myostatin blocker’ supplement was being released, clinical trials of a drug known as Stamulumab3 developed by well known drug company Wyeth was being conducted. As the aim of the experiment was to view the drugs safety rather than its efficacy, it is hard to extrapolate any evidence for its effectiveness. Wyeth however is continuing its research into myostatin inhibiting drugs. Another drug was being developed at the same time called ACVR2B4 which was able to block myostatin by preventing it attaching to other molecules which started its action. The problem with drugs however is that generally, continual doses are required in order to sustain the effect. A much more effective way to ensure long term success is to use gene therapy. In this case, you can either completely block the gene that expresses myostatin or you can upregulate the genes that encode follistatin (another protein that blocks myostatin). This last idea was proven successful in experimental studies conducted on monkeys conducted in 20095.

The Future of Myostatin

So what does the future hold for myostatin blockers? Eventually, this author has no doubt that drugs will be produced which can essentially block the action of myostatin. Of course this reality is still quite far away considering the hurdles involved in human clinical trials. Another problem is the long term safety of these drugs including possible side effects. The potential of gene therapy and its ability to block the action of myostatin is definitely the future of research. However, whenever a new form of performance enhancement becomes available, so too are the procedures to detect it. While gene doping is still relatively new, WADA has already funded a project which is able to detect gene doping up to 56 days post procedure6. Furthermore, some scientists are worried about one potential implication of blocking the action of myostatin. Myostatin is believed to keep our satellite cells in a state of hibernation until it is required. By blocking myostatin, we run a real risk of depleting our satellite cells early in life which can have implications as we age. Regardless of the potential risks, continuing research into myostatin and its inhibition is certainly an interesting area which can potentially have some substantial impacts in both the clinical, normal and athletic populations.

1 Ramazanov Z, Jimenez del Rio M, Ziegenfuss T. ‘Sulfated polysaccharides of brown seaweed Cystoseira canariensis bind to serum myostatin protein.’ Acta Physiol Pharmacol Bulg. 2003;27(2-3):101-6.
2 Willoughby DS. ‘Effects of an alleged myostatin-binding supplement and heavy resistance training on serum myostatin, muscle strength and mass, and body composition.’ Int J Sport Nutr Exerc Metab. 2004 Aug;14(4):461-72.
3 Wagner KR, Fleckenstein JL, Amato AA, Barohn RJ, Bushby K, Escolar DM, Flanigan KM, Pestronk A, Tawil R, Wolfe GI, Eagle M, Florence JM, King WM, Pandya S, Straub V, Juneau P, Meyers K, Csimma C, Araujo T, Allen R, Parsons SA, Wozney JM, Lavallie ER, Mendell JR. ‘A phase I/IItrial of MYO-029 in adult subjects with muscular dystrophy.’ Ann Neurol. 2008 May;63(5):561-71.
4 http://www.mdausa.org/research/060106myostatin_blocker.html. Last accessed 30th June 2011
5 Kota J, Handy CR, Haidet AM, Montgomery CL, Eagle A, Rodino-Klapac LR, Tucker D, Shilling CJ, Therlfall WR, Walker CM, Weisbrode SE, Janssen PML, Clark KR, Sahenk Z, Mendell JR, Kaspar BK (2009). "Follistatin Gene Delivery Enhances Muscle Growth and Strength in Nonhuman Primates". Science Translational Medicine 1 (6): 6ra15–6ra15.
6 T Beiter, M Zimmermann, A Fragasso, J Hudemann, A M Niess, M Bitzer, U M Lauer and P Simon. ‘Direct and long-term detection of gene doping in conventional blood samples.’ Gene Therapy 18, 225-231 (March 2011) | doi:10.1038/gt.2010.122
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