AOD 9604

GOALS TREATED:
Muscle Gain

Fat Loss
Injury Rehabilitation
Anti-ageing
Libido
Tanning  
AOD 9604: A Powerful Peptide for Fat Loss and Cartilage Regeneration

Overview

AOD 9604, or Anti-Obesity Drug 9604, is a synthetic peptide developed as a targeted fat-loss therapy. Derived from a modified fragment of human growth hormone (HGH), this peptide aims to enhance fat metabolism without impacting insulin sensitivity or appetite. Unlike traditional weight-loss medications, AOD 9604 works by accelerating metabolic rate, promoting lipolysis, and inhibiting lipogenesis, all without affecting lean muscle mass.

Key Benefits of AOD 9604

  • Promotes Fat Burning: Stimulates lipolysis, allowing for fat release from fat cells.
  • Inhibits Fat Storage: Prevents new fat formation through anti-lipogenic effects.
  • Supports Cartilage and Joint Health: Shown to enhance cartilage regeneration and may benefit conditions such as osteoarthritis.
  • No Impact on Blood Sugar Levels: Does not elevate blood glucose or insulin levels, offering a safer alternative to traditional growth hormone therapy.
  • Safe and Targeted Action: Minimal side effects and no stimulation of Insulin-like Growth Factor 1 (IGF-1), which avoids risks associated with typical growth hormone therapies.

How It Works

AOD 9604 consists of amino acids 177-191 from the growth hormone molecule, known to specifically target fat breakdown (lipolysis). By bypassing the HGH receptor, AOD 9604 independently stimulates fat metabolism and prevents fat formation. In animal studies, this peptide has demonstrated consistent fat reduction even in cases without beta-3 adrenergic receptors, suggesting multiple pathways involved in its mechanism.

Clinical Applications

  • Weight Management: Primarily used to aid fat loss without influencing appetite or muscle mass.
  • Joint and Cartilage Regeneration: Studies indicate that AOD 9604 may aid cartilage repair and mitigate joint pain, particularly when used alongside hyaluronic acid.
  • Metabolic Health: By not affecting insulin sensitivity, AOD 9604 may benefit those at risk for metabolic conditions while supporting healthy body composition.

Research and Evidence

AOD 9604 and Fat Loss

Clinical trials conducted on both animals and humans have revealed significant fat-loss potential for AOD 9604:

  • Animal Studies: Early studies in obese mice showed marked fat reduction and weight loss with no effect on food intake.
  • Human Trials: In a 12-week study with 300 obese adults, AOD 9604 demonstrated consistent weight loss, with participants in the lowest dose group losing an average of 2.8 kg.

Cartilage and Joint Regeneration

Research has shown that AOD 9604 may support cartilage health:

  • Cartilage Regeneration: A study in rabbits treated with AOD 9604 and hyaluronic acid revealed enhanced cartilage regeneration, suggesting the peptide’s potential for joint repair.
  • Osteoarthritis Relief: AOD 9604 has been shown to reduce inflammation and improve joint function, making it a promising candidate for osteoarthritis treatment.

Heart and Metabolic Health

By aiding fat metabolism, AOD 9604 indirectly supports heart health. Studies suggest that, beyond its fat-reduction properties, AOD 9604 may improve metabolic markers associated with cardiovascular health.

Dosage and Administration

  • Weight Management: Inject 0.2 ml (300 μg) subcutaneously daily for 20 days.
  • Cartilage and Joint Health: Inject 0.3 - 0.5 ml (500-750 μg) intra-articularly once a week for 4 weeks, then once a month for five months.
  • Storage: Store frozen until first use; once opened, refrigerate at 2°C - 8°C, where it remains stable for 60 days.

Side Effects and Safety

AOD 9604 has shown a strong safety profile in studies, with most users experiencing minimal side effects. Notable Safety Features:

  • No Increase in Appetite or Blood Glucose: Does not impact blood sugar levels, unlike some other peptides.
  • Low Risk of Antibody Formation: Due to its similarity to natural HGH, AOD 9604 is less likely to trigger an immune response.
  • No IGF-1 Stimulation: By not increasing IGF-1 levels, AOD 9604 avoids potential risks like joint stress or glucose intolerance.

Product Information

  • Product Name: AOD 9604 (1500 μg/ml, 4 ml vial)
  • Supplied As: Injectable peptide
  • Suggested Usage: For those focused on fat reduction or joint health; recommended use in cycles for optimal results.
Research and Clinical Studies

AOD 9604 Peptide Chronic Use and Lipolytic Activity

Early clinical studies were carried out on obese mice where the AOD 9604 peptide was chronically administered for 14 days. Following the experiment, the results reported reduction in body weight and excess fat. These results were directly correlated with the increased levels of major lipolytic receptors called ß3-AR cells found in the fat cells. AOD 9604 peptide has appeared to exhibit effects similar to hGH where both are capable to increase the repressed levels of lipolytic receptors in obese mice as compared to the lean mice. To confirm whether the lipolytic effects of AOD 9604 were merely associated with the increased lipolytic receptor levels, additional studies were carried out where AOD 9604 was administered to mice with knocked out lipolytic receptors. Interestingly, AOD 9604 was reported to be apparently effective in this case as well. Further analysis suggested that the AOD 9604 peptide enacted the lipolytic effects via increased energy expenditure and fat oxidation. Thus, it was concluded that AOD 9604 may be effective in fat reduction irrespective of the receptors, though these studies have shown AOD 9604 peptides to increase the lipolytic receptor expression. (1) Both these findings on chronic and acute use of AOD 9604 illustrated that while enhanced ß3-AR expression played a vital role in the chronic effectiveness of the compound, ß3-AR was not the sole arbiter in this reaction. Oxidation and enhanced energy expenditure appeared to be vital in the apparent efficacy of the peptide.

In 2000, a research study was carried out in obese Zucker rats where the AOD 9604 peptide was administered daily for 19 consecutive days. Post treatment, it was reported that the body weight appeared to be reduced in all rats by over 50% in comparison to the rats treated with placebo. Further analysis suggested that the adipose tissues of the AOD 9604 peptide treated animals had increased lipolytic activity and there was no adverse impact on the insulin sensitivity of the animals.

AOD 9604 Peptide and Obesity

In 2004, Metabolic Pharmaceuticals Limited conducted clinical trials where 300 obese patients were given the peptide for a 12-week period. Five gradually increasing dosages were used, alongside a placebo. Out of all, the group administered with the lowest dose showed the best results, with an average weight loss of 2.8 kilograms over the 12 week period. The rate of weight loss remained consistent throughout the treatment period. The trial results noted minor improvement exhibited in the patients’ cholesterol profiles and glucose tolerance levels. This suggested the peptide’s promise in long-term dosing therapies for lowering and sustaining weight. (4)

AOD 9604 Peptide and Cell Regeneration

Additional research was conducted to study the regenerative effects of the peptide. In 2015, 32 white rabbits were divided into four groups of eight and each group was administered with a placebo,  AOD 9604, hyaluronic acid, or a combination of both AOD 9604 and hyaluronic acid for a period of 4 to 7 weeks. After treatment, these rabbits were assessed morphologically and histopathologically to determine the degree of cartilage degeneration. It was concluded that rabbits treated with the combination dose of AOD 9604 with hyaluronic acid apparently exhibited the least degeneration. Thus, it was suggested that AOD 9604 has potential to enhance cartilage regeneration and cartilage repair in some capacity. (3) Multiple clinical studies in humans have further suggested that the peptide may significantly induce lipolysis and prevent lipogenesis by mimicking the natural hGH that regulates the body fat without the unwanted side effects on blood sugar and insulin levels. Additionally, this peptide has been reported to exhibit potential in cell repair, and bone and cartilage regeneration.

AOD9604 is a modified version of the hGH fragment 176-191 peptide (contains a di-sulfide bridge) and thus a derivative of human growth hormone (hGH). Originally developed as a lipolytic (fat burning) compound, AOD9604 has shown benefit in studies of heart disease, osteoarthritis/cartilage repair, and metabolic syndrome. AOD9604 stimulates lipolysis (the breakdown or destruction of fat) and inhibits lipogenesis in animal studies.

What is AOD9604?

AOD9604 is a modified version of fragment 176-191, which is itself a smaller, modified piece of human growth hormone (HGH). AOD9604 was originally developed as an anti-obesity drug due to its lipolytic (fat burning) properties. This peptide is valued for the fact that it has limited effects beyond fat burning. It does not appear to affect IGF-1 levels or insulin levels and therefore is not a risk factor in promoting glucose intolerance or diabetes[1]. There is also no evidence that the body forms antibodies against AOD9604 as it is similar enough in structure to HGH to avoid stimulating an immune system response[2

Sequence: Tyr-Leu-Arg-Ile-V yr-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-V al-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe al-Glu-Gly-Ser-Cys-Gly-Phe Disulfide bridge Disulfide bridge Cys7-Cys15

Molecular Formula: C78H123N23O23S2

Molecular Weight: 1815.12 g/mol

PubChem CID: 16131447

CAS Number: 386264-39-7

AOD9604 Research 1. AOD9604 and Obesity AOD9604 was originally developed as an analogue of HGH with the express purpose of fighting fat. Phase 2b clinical trials were completed in Australia testing the drug in 300 obese individuals. The results of once daily administration of the peptide for 12 weeks showed that the drug tripled weight loss when compared to placebo and that the rate of weight loss remained steady during the trial period[3], [4]. This latter fact indicates that a resistance to the peptide is unlikely to arise and that longer-term treatment would result in even greater weight loss. Research in mice that are genetically prone to obesity indicates that AOD9604 most likely does not work only by affecting the beta-3-adrenergic receptors found on white fat. It was originally speculated that the peptide bound to these receptors and increased the rate of metabolism in fat cells, shifting them from a storage mode to a usage mode. It turns out that even in mice that lack these receptors, fat loss takes place when AOD9604 is administered[5]. Though the beta-3- adrenergic receptor likely plays a role in fat loss secondary to AOD9604, at least one other mechanism must be in play as well. There is some thought that AOD9604 may indirectly activate apoptosis in white fat cells.

Joint Pain and Function

Research in rats indicates that injections of AOD9604 directly into arthritic joints can work in synergy with existing therapies to improve pain, reduce disability, and improve quality of life[6] . Changes in both gross clinical exam and microscopic structure of cartilage in the affected joints indicates that AOD9604 is effective in treating the root cause of osteoarthritis and may work as both a treatment and preventative. Though AOD9604 is effective in reducing joint dysfunction on its own, it works better in combination with other therapies. It isn’t clear how the synergy arises, but additional research using the peptide may reveal novel pathways for improving cartilage growth, a notoriously challenging clinical problem. 3. AOD9604 and Heart Disease Though fat reduction and weight loss directly reduce the risk of heart disease, there is evidence to suggest that AOD9604 has beneficial effects on the heart beyond its ability to reduce fat burden. It is thought that the peptide may directly affect metabolism in such a way to reduce complications separate from its effects on obesity. This is not unheard of, as drugs like pioglitazone and acipimox both reduce metabolic complications without treating obesity at all. It is thought that the secondary pathway by which AOD9604 causes fat loss, the pathway that is independent of beta3-adrenergic receptor activation, may play a role in improving metabolic metrics even while it boosts fat loss[7] . AOD9604 exhibits minimal side effects, high oral and excellent subcutaneous bioavailability in mice. Per kg dosage in mice does not scale to humans.

Referenced Citations

Referenced Citations [1] F. M. Ng, J. Sun, L. Sharma, R. Libinaka, W. J. Jiang, and R. Gianello, “Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone,” Horm. Res., vol. 53, no. 6, pp. 274–278, 2000. [PubMed]

[2] H. Stier, E. Vos, and D. Kenley, “Safety and Tolerability of the Hexadecapeptide AOD9604 in Humans,” J. Endocrinol. Metab., vol. 3, no. 1–2, pp. 7-15–15, Apr. 2013. [Journal of Endocrinology & Metabolism]

[3] “Obesity drug codenamed AOD9604 highly successful in trials,” News-Medical.net, 16-Dec-2004. [Online]. Available: https://www.news-medical.net/news/2004/12/16/6878.aspx. [Accessed: 24-May-2019].

 [4] R. Zieba, “[Obesity: a review of currently used antiobesity drugs and new compounds in clinical development],” Postepy Hig. Med. Doswiadczalnej Online, vol. 61, pp. 612–626, Oct. 2007. [PubMed]

[5] M. Heffernan et al., “The Effects of Human GH and Its Lipolytic Fragment (AOD9604) on Lipid Metabolism Following Chronic Treatment in Obese Mice andβ 3-AR Knock-Out Mice,” Endocrinology, vol. 142, no. 12, pp. 5182–5189, Dec. 2001. [PubMed]

 [6] D. R. Kwon and G. Y. Park, “Effect of Intra-articular Injection of AOD9604 with or without Hyaluronic Acid in Rabbit Osteoarthritis Model,” Ann. Clin. Lab. Sci., vol. 45, no. 4, pp. 426–432, Jul. 2015. [PubMed]

 [7] M. D. Jensen, “Potential role of new therapies in modifying cardiovascular risk in overweight patients with metabolic risk factors,” Obes. Silver Spring Md, vol. 14 Suppl 3, pp. 143S-149S, Jun. 2006. [Wiley Online Library]

[8] STIER, H., VOS, E., KENLEY, D.. Safety and Tolerability of the Hexadecapeptide AOD9604 in Humans. Journal of Endocrinology and Metabolism, North America, 3, apr. 2013. Available at: .