Quick AOD9604 Summary Points
- AOD9604 is an anti-obesity peptide based on human growth hormone
- AOD9604 comes in the form of an ingectable medicine or transdermal cream
- AOD9604 was originally developed after research on mice, but subsequent studies in human have shown no efficacy
AOD9604 – What is it?
AOD9604 is a peptide (a chain of amino acids) which was developed and patented by a company called Metabolic Pharmaceuticals in Australia in the late 1990s. AOD stands for "Anti Obesity Drug". This peptide has an amino acid sequence that mimics the lipolytic region of human growth hormone (the region of this hormone thought to be responsible for burning fat) and it has been promoted variously as a weight loss supplement, as an aid to muscle and cartilage repair, and a treatment for osteoarthritis by its manufacturers. It is also known as lipotropin and Tyr-hGH fragment, and is generally available these days as a transdermal cream or an injectable.
AOD9604 - Why do people use it?
AOD9604 is promoted heavily by various manufacturers as a substance that is able to burn fat and assist in the repair of muscle and cartilage. The fact that this product derives from, and claims to mimic the effects of a powerfully anabolic banned substance provides a psychological incentive to many potential users, as does the attention drawn by the AFL "peptides" scandal of early 2013 and the subsequent report by the Australian Crime Commission (1).
Whilst AOD9604 is not approved by the Australian TGA, it can be legally obtained on a doctor's prescription and dispensed by a compounding pharmacy (2). This is true of many experimental substances, but it does big favours for the reputation of AOD9604, giving the impression that, like other drugs issued by the medical profession, it is an efficacious and high quality product. These reasons, when considered together, give a powerful impression that peptides are highly effective – they wouldn't ban them for no reason, would they?
Metabolic Pharmaceuticals have reported that recent in vitro trials have shown that AOD9604 may stimulate the growth of bone cells, and muscle and cartilage cells. These results have not yet been reproduced in animals or humans (4). There was a lot of speculation that Metabolic was providing AOD9604 to players at the Essendon Football Club as part of a secret clinical trial, but the company has flatly denied this claim, claiming it has not run any human trials since 2007 (2). AOD9604 has been scientifically proven safe and side-effect free (2), and is apparently very difficult to detect in the blood.
AOD9604 – The Negatives
The biggest negative, and this is a big one, is that AOD9604 has undergone very rigorous scientific testing, and has been found to have no effect in humans (3). When AOD9604 was first developed, it showed significant promise as a weight loss treatment. A special strain of obese mice supplemented with the peptide showed a reduction in weight, increased fat oxidation, and raised plasma glycerol, which are indicators of lipolysis, or fat burning (5). Subsequent studies in obese mice and rats attempted to show that the peptide works to burn fat in the same way as human growth hormone, but found that this was not the case, meaning that the fact this peptide resembled hGH was meaningless. Scientists were unable to determine how this peptide was working in mice (6).
Metabolic turned their attention to human studies and performed six clinical trials on 925 people between 2001 and 2007. Not one of these trials showed that AOD9604 caused any weight loss or changes in body composition (3). In 2007, the company that owns Metabolic, Calzada, reported to their shareholders that AOD9604 showed no promise, and was being abandoned as a weight loss drug (2,3). The failure was blamed on inefficient absorption of the peptide drug through oral administration, as was used in the trials, even though rodent studies had shown the oral delivery route to be effective. At this point, Metabolic had sunk a massive $50 million into development and trials of AOD9604.
In 2010, the company heard word that bodybuilders were importing knock-off versions of the patent-protected peptide from China, and started licensing the manufacturing rights out to other companies in an attempt to compete, as this was determined to be a better course of action than attempting to sue the Chinese company for patent breach (7, 8). Desperate to recoup this investment, they invested a small additional amount into developing a technology that allowed the peptide to be absorbed through the skin, in collaboration with a company called Phosphagenics (4). The peptide was then licensed for use in BodyShaper, an anti-cellulite cream. Phosphagenics later dropped AOD9604 from BodyShaper, citing excessive expense and ineffectiveness (3).
When the AFL Peptides scandal hit, Calzada was forced to clarify the facts about AOD9604, and put out a cleverly worded press statement aimed at potential investors, concentrating on the fact that AOD9604 had been proven safe in large scale clinical trials (neglecting to mention a lack of effectiveness) and spoke of the success of AOD9604 on stimulating bone growth, and on cartilage and muscle cell repair in in-vitro trials (2,4). The black market uses for this peptide in muscle repair and treatment of obesity were also mentioned in the release, and it is clear through media reports on this scandal that Calzada gained traction from the profile boost (8).
If there's one thing that science has definitively said about AOD9604, it is that it is safe and has no side effects. Calzada, after trying the peptide out as an anti-obesity and anti-arthritic, has succeeded in having the peptide declared "Generally regarded as safe" by the FDA, which makes it legal to use as a food additive in America. Calzada, seemingly under no pretense that their product has pharmaceutical properties, is now trying to break into the US over the counter supplement and "Nutraceutical" market with AOD9604 (2,4). Interestingly, the compound has only been approved for use in levels of up to 1mg per day (2), whereas the doses used in trials generally hovered around 500ug/kg (5,6), which means a 100kg person was receiving 50mg of the peptide daily. There is no science behind the peptide, or the dosage, and Calzada themselves have previously said AOD9604 is not effective orally (2).
Press coverage and word of mouth has generated quite a bit of hype around AOD9604. Despite its popularity on the black market, there is no research into the safety and effect of injecting this peptide at high doses. Intriguingly, it is not currently in Calzada's interest to fight the black market production of AOD9604, even though it is a patented product. Calzada lack the funds to legitimately boost the reputation of this peptide through clinical trials, and there is a strong chance these would once again prove that AOD9604 has no effect. The good reputation this peptide currently enjoys is likely to provide strong leverage to its marketing as a food supplement in the United States.
AOD9604 Legal Status
Whilst not illegal to buy AOD9604 in Australia, AOD9604 does not have approval by the TGA, which means it is not allowed to be sold on the basis of it having any pharmaceutical or performance enhancing benefits. It has not been approved by any pharmaceutical authority worldwide, except for the previously mentioned "Generally Regarded As Safe" designation by the FDA. AOD9604 is currently classed by the World Anti Doping Agency (WADA) as a non-approved substance, which means it is not legal for use by athletes in competition. WADA policy is to ban all substances that are suspected of being performance-enhancing, even in the absence of clinical proof (1,2).
There are many legal, cheap and effective alternatives for anyone looking to lose weight and bulk up. One of the most popular products at Mr Supplement is Elemental Nutrition's HGH, a natural supplement designed to maximise the body's own production of growth Hormone. Pair a good quality fat loss protein with a solid training regime and you cannot go wrong. BSc Hydroxyburn is a lean protein with added fat loss ingredients that ticks all the boxes. Another natural hormonal option is a testosterone booster. Massive Muscle Fuel is known as the strongest legal alternative to anabolic steriods, and is not for the fainthearted.
(1) Performance and Image-enhancing substances. Australian Crime Commission. http://www.crimecommission.gov.au/publications/other-publications/organised-crime-drugs-sport/performance-image-enhancing-substances Accessed 3rd December 2013
(2) "AOD9604 – Important Clarifications" Calzada, 26th April 2013. http://www.asx.com.au/asxpdf/20130426/pdf/42fh15rvm7p65t.pdf Accessed 4th December 2013
(3) Much ado about nothing: The peptide they say never worked. Natasha Wallace. http://www.smh.com.au/sport/much-ado-about-nothing-the-peptide-they-say-never-worked-20130802-2r4ug.html Accessed 3rd December 2013
(4) Calzada Limited – Metabolic. http://calzada.com.au/metabolic-pharmaceuticals-pty-ltd/ Accessed 4th December 2013
(5) Heffernan MA, Thorburn AW, Fam B, Summers R, Conway-Campbell B, Waters MJ and NG FM. 2001a. International Journal of Obesity. 25: 1442-1449. Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment.
(6) Heffernan M, Summers R, Thorburn A, Ogru E, Gianello R, Jiang W-J and Ng FM. 2001b. Endocrinology. 142(12): 5182-5189. The effects of human GH and its lipolytic fragment (A)D9604) on lipid metabolism following chronic treatment in obese mice and β3-AR knock-out mice.
(7) Boreham T. Bulk up on this fat fighting firm (Calzada). March 2 2010. http://www.theaustralian.com.au/business/opinion/bulk-up-on-this-fat-fighting-firm-calzada-czd-35c/story-e6frg9lo-1225835816678 Accessed 4th December 2013
(8) Fat fighting firm worth a guernsey. April 12 2013. http://www.theaustralian.com.au/business/opinion/fat-fighting-firm-worth-a-guernsey/story-e6frg9lo-1226618621089# Accessed 4th December 2013