Some Pep in Your Step: Are Peptide Drugs the Future of Doping?

       If you watched the Winter Olympics this year you probably sat through dozens of TV segments detailing the nightmare that is doping. The fact that this nightmare is a fantasy having very little to do with actual doping is laughable, but we won't be discussing it today. Instead we'll take a look at one of the monsters from the current doping nightmare model being spoon fed to the public: peptides.

       During the Olympics peptide drugs were both lamented and praised as the "next big thing" in doping, and following the games Average Joe Juicehead has decided he must have this new toy. Forum discussions are overflowing with references to poorly written articles by drug dealers seeking to cash in on the trend. Bros the world over see this and begin clamoring for this undetectable drug that is supposedly going to change the game, and they are pumping their misunderstandings back into the discourse as quickly as their gurus can come up with new sermons. But the discourse isn't limited to the inevitable herd of idiots. The serious doping community - comprised of elite athletes, coaches, physicians, and scientists - is paying attention as well. And while the discussion among these folks is evidence-based and the science is applied by professionals the rest of the scientific and sporting communities are left largely in the dark, preferring to avoid the ethical pitfalls of getting involved with such a taboo.  The result is the normal mixture of guruism, confusion, broscience, and nuggets of good data so familiar to those seeking to study such matters informally. The consensus is that peptide drugs are the future of doping. But are they? Yes. Definitely yes. But not in the way you imagine.

       You see, peptide drugs aren't new. They've been around longer than you have, and they've been in the drug stacks of athletes since their inception. A peptide is simply a group of amino acids bound together to produce a chain. For the science-minded note that the carboxyl group of one amino acid will bind covalently with the amine group of the next amino acid in the chain. The resulting polymer can take on many roles. Some act as hormones, and these are the ones that interest us today. Notable peptide drugs include insulin, IGF-1, growth hormone, and the various growth hormone releasing peptides. As you see, peptide drugs have been around. Insulin and GH transformed bodybuilding in the 1980s and 1990s but both were in use before that. GHRP was discovered in 1976, and was immediately noted for its ergogenic effects. It's difficult to call something the future when it's been making waves since the era of free love. At the same time, understanding has improved, accessibility is exponentially greater, and the information age has made doping secrets into reality TV. So while peptide drugs are long-established their popular use is relatively recent. Let's take a look at the big names in peptide doping, and summarize each.

• Growth Hormone: Just about everyone is aware of GH. Arnold and his contemporaries were harvesting it from cadavers and synthetic GH was responsible for many of the conditioning changes bodybuilding underwent in the 80s. Outside of physique sports, it has gained a following as an anti-aging medicine, rehab aid, and fat loss aid. While its anabolic effects are debatable and its benefits as an ergogen are exagerrated GH remains popular and will continue to have a place in doping because of its other effects. This link does a good job explaining things. http://bjsportmed.com/content/37/2/100.full
• Insulin: There is a lot of debate on how insulin acts as an anabolic, but it clearly does. One one side, it is claimed that the anabolic effect is due to inhibition of proteolysis (http://www.ncbi.nlm.nih.gov/pubmed/16705065) while the other camp promotes the idea that protein synthesis is stimulated by insulin when sufficient levels of amino acids are supplied(http://www.ncbi.nlm.nih.gov/pmc/articles/PMC295560/). Insulin is also the most dangerous peptide drug, and it has the distinction of being the only hormonal PED that can kill you via a direct action of the drug. Too much insulin can result in insulin shock, potentially driving glucose levels down low enough for you to lose consciousness and incur brain damage. I'm not trying to be alarmist here. I am generally fairly pro-doping. But danger is danger, and risk from insulin use absolutely must be acknowledged. Oddly, however, this drug is available over the counter in every state in the USA and in most other developed countries. In fact all the drugs below are completely legal to buy, possess, and use in most countries.
• Insulin-like Growth Factor 1: IGF-1, so named for its similarity to insulin and its ability to interact with the insulin receptor, is a major driving force in growth and development and mediates the growth effects of GH by stimulating proliferation and differentiation of satellite cells. GH stimulates its production in the liver and other tissues secrete specific types as well. There are multiple variants, and the functions are simply too many to list in a concise summary. http://mp.bmjjournals.com/content/54/5/311.full
• Mechano Growth Factor: MGF is a synthetic variant of IGF-1 which mimics (or nearly so) the action of IGF-1 Ec, the variant produced by exercising or severely stressed muscle tissue. It acts in a regenerative and growth-promoting capacity in local tissues. This is the peptide grabbing the headlines, as it's been revealed that many athletes in the recent Olympic Games were using it both as an ergogen leading up to the events and as a rehabilitative aid for injuries sustained during competition. I will avoid dropping names, but I can tell you that some very prominent athletes are practically marinating in MGF. http://bjsm.bmj.com/content/39/11/787.full
• Growth Hormone Releasing Hormone: GHRH is pretty straightforward. It interacts with the anterior pituitary to signal release of GH. (http://www.clinchem.org/content/36/3/415.full.pdf+html) The synthetic analog CJC 1295, also called Mod GRF 1-29, is modified via a process known as bioconjugation to extend active life. It is an effective GH releaser on its own (http://press.endocrine.org/doi/abs/10.1210/jc.2005-1536) but works synergistically with Growth Hormone Releasing Peptides (discussed below) to produce GH pulses of greater magnitude than is possible with either alone.  http://europepmc.org/abstract/MED/8421084
• Growth Hormone Releasing Peptides: GHRPs are growth hormone secretagogues acting separately from Growth Hormone Releasing Hormone on the pituitary gland and hypothalamus to initiate secretion of GH. For decades, the mechanism of action was unclear, but we now know these drugs mimic the action of ghrelin, most well-known for it's regulation of hunger. The most common growth hormone secretagogues taking peptdide form are GHRP-2, GHRP-6, ipamorelin, and hexarelin. Each has unique aspects.  http://link.springer.com/chapter/10.1007/978-1-4612-2396-2_11

       As evidenced by the linked literature peptides are well-established in both the scientific community and the doping community, with a long history of use as ergogens in both clinical and sporting settings. Their actions do not rely on androgens, making them valuable additions or alternatives to androgen-derived steroid drugs in circles where use  of ergogenic aids is common. Many of the side effects associated with steroids can be avoided with peptides, many peptides are legal, and increasing connectivity via the internet makes access increasingly easy for would-be users. Concurrently, advances in our understanding and technological ability will lead to continous improvements in both quality and use of these drugs. All these factors make peptides the force they are today, and will continue to contribute to their popularity in the future.