AOD9604

AOD9604 is a synthetic peptide derived from human growth hormone (hGH), specifically designed to mimic its fat-burning properties. Developed in the late 1990s by Metabolic Pharmaceuticals in Australia, AOD9604 consists of a modified fragment of the C-terminal region of hGH (amino acids 177-191) with an additional tyrosine residue at the N-terminus. Originally intended as an anti-obesity drug, it has since been explored for various therapeutic applications.

Category

Lipolytic peptide fragment of HGH

Sequence

H-Tyr-Leu-Arg-Ile-Val-Gln-Cys(1)-Arg-Ser-Val-Glu-Gly-Ser-Cys(1)-Gly-Phe-OH

Molecular Weight

Approximately 1815.1 g/mol

Molecular Formula

C78H123N23O23S2

Half Life

Approximately 4 minutes in serum

Most Common Uses

AOD9604 is explored for diverse applications in the medical and wellness fields. It is primarily studied for supporting weight management by promoting fat breakdown and enhancing metabolism, making it a promising candidate for obesity treatment. Researchers also investigate its potential to improve metabolic health, including insulin sensitivity and lipid profiles, which may benefit those with metabolic syndrome. It shows promise in joint and tissue repair, particularly for cartilage regeneration in osteoarthritis, due to its anti-inflammatory effects.

In sports science, it attracts interest for improving body composition and recovery without the growth-promoting effects of full hGH, appealing to athletes under regulatory oversight. AOD9604 is also used in cosmetic contexts for potential anti-aging benefits, such as enhancing skin elasticity and reducing fat. While these uses stem from ongoing research, regulatory approval and broader adoption depend on further evidence of efficacy and safety.

Mechanism of Action

AOD9604 functions by mimicking the fat-burning properties of its parent molecule while avoiding growth-promoting effects. It stimulates lipolysis, the process of breaking down stored fat into free fatty acids and glycerol, primarily in adipose tissue. This occurs through interaction with specific receptors on fat cells, which activates intracellular pathways that enhance lipid metabolism. AOD9604 also appears to inhibit lipogenesis, the formation of new fat, thereby promoting a net reduction in fat mass.

Additionally, research suggests it may influence metabolic processes by improving insulin sensitivity and lipid profiles, potentially benefiting conditions like metabolic syndrome. In preclinical studies, particularly in osteoarthritis models, AOD9604 demonstrates anti-inflammatory effects and supports cartilage repair, likely through modulation of inflammatory mediators and tissue regeneration pathways. These mechanisms collectively contribute to its potential in weight management, metabolic health, and tissue repair, though further studies continue to clarify its precise molecular interactions.

Structure and Pharmacology

AOD9604 is a synthetic peptide comprising 16 amino acids, derived from the lipolytic C-terminal region of human growth hormone (hGH), specifically residues 177–191 with an additional tyrosine at the N-terminus. Its sequence, H-Tyr-Leu-Arg-Ile-Val-Gln-Cys(1)-Arg-Ser-Val-Glu-Gly-Ser-Cys(1)-Gly-Phe-OH, features a cyclic disulfide bridge between cysteine residues at positions 7 and 14, which stabilizes its structure. With a molecular weight of 1815.1 g/mol and a molecular formula of C78H123N23O23S2, AOD9604 is designed to retain the fat-metabolizing properties of hGH while eliminating growth-promoting effects.

Pharmacologically, AOD9604 promotes lipolysis in adipose tissue by interacting with receptors that trigger intracellular pathways, releasing free fatty acids and glycerol for energy use. It also appears to suppress lipogenesis, limiting new fat formation.

Studies indicate a short serum half-life of approximately 4 minutes in rat plasma, though oral administration in pigs shows slower degradation patterns.

Additionally, AOD9604 exhibits anti-inflammatory effects and supports cartilage repair in preclinical models, suggesting broader applications in metabolic and musculoskeletal health. Its pharmacokinetic profile includes rapid clearance, necessitating specific dosing strategies to maintain efficacy, with ongoing research exploring its therapeutic potential and safety.

Dosages

AOD9604 has been administered in various dosages across clinical and preclinical studies, primarily for weight management and metabolic health research. In human clinical trials, typical dosages range from 0.25 mg to 1 mg per day, often delivered via subcutaneous injection to optimize bioavailability.

For instance, studies investigating its effects on obesity have used daily doses of 1 mg, administered consistently over weeks to months, with adjustments based on patient response and tolerability. Oral formulations, tested in some trials, involve higher doses, such as 9 mg daily, due to lower absorption efficiency in the gastrointestinal tract.

Warnings and Cautions

AOD9604 requires careful consideration due to its experimental status and limited regulatory approval. People should avoid its use without medical supervision, as its safety profile remains under investigation. Clinical trials have reported mild side effects, such as headaches, nausea, and injection site reactions, but long-term effects are not fully understood. Those with pre-existing conditions, particularly metabolic or endocrine disorders, should exercise caution, as AOD9604 may influence insulin sensitivity or lipid metabolism in unpredictable ways. Pregnant or breastfeeding women should refrain from use, as no studies have established its safety in these populations.

Additionally, its use in athletic settings may conflict with anti-doping regulations, given its derivation from human growth hormone, potentially leading to sanctions in competitive sports. Interactions with other medications or supplements are still poorly studied, so they should be avoided. As research continues, people should rely on evidence-based guidance and avoid unverified sources of AOD9604 to minimize potential risks.

Research & Clinical Trials

A Promising Safe Treatment for Obesity

The study showed that AOD9604, a lab-made version of a fat-burning part of human growth hormone, had strong effects against obesity in overweight lab rats. The rats were given the compound by mouth each day for 19 days at a specific dose, and they gained over 50% less weight compared to untreated rats. This weight difference was linked to a clear increase in fat breakdown in their body fat.

Safety and Tolerability in Preclinical Studies

The study concluded that AOD9604 is safe and well-tolerated based on a comprehensive set of non-clinical tests. It showed no evidence of genotoxicity in standard assays, including the Ames test, chromosomal aberration assay, and bone micronucleus assay, indicating that it does not cause DNA mutations or structural damage.

Long-term toxicology studies in rats (over six months) and monkeys (over nine months) revealed no toxic effects, even at high oral doses. Pharmacokinetic studies demonstrated that AOD9604 is well absorbed when taken by mouth, rapidly broken down in the body, and distributes similarly across organs regardless of whether administered orally or by injection. No immune responses or adverse clinical signs were observed in any animal models.

Effects of hGH and AOD9604 on Lipid Metabolism

The study concluded that both human growth hormone (hGH) and its smaller fragment AOD9604 can help obese mice lose weight and body fat after 14 days of treatment. This effect is linked to an increase in a specific signal (called β3-adrenergic receptor RNA) that plays a major role in breaking down fat.

AOD9604 Injection Effects in Rabbit Osteoarthritis

The study showed that injecting AOD9604, a lab-made version of a small part of human growth hormone, directly into the knee joint helped heal damaged cartilage and improve movement in rabbits with osteoarthritis (OA). Rabbits that got AOD9604 did better than those treated with just salt water (saline), and had similar or slightly better results than those given hyaluronic acid (HA), a substance commonly used to treat joint problems. However, the best results came from the group that received both AOD9604 and HA together. These rabbits had the least cartilage damage, the mildest tissue changes under the microscope, and recovered from limping the fastest. The combination worked better than either treatment alone, both in protecting the joint structure and helping the animals move more easily.

Detailed tissue checks showed that the combination treatment greatly reduced surface damage, cartilage wear, and cell disruption in the joints. The treated joints looked nearly normal and were well-organized, suggesting that this approach could possibly reverse cartilage damage caused by OA. The results also showed that AOD9604 not only helps protect and repair joint cartilage, but also boosts the effect of HA, which is already used for joint care. Because AOD9604 does not trigger the production of IGF-1 (a hormone linked to side effects like tumors or blood sugar issues), it may be a safer option than regular growth hormone treatments.

Sourcing

USA

LIMITLESS LIFE NOOTROPICS aka Biotech

Use Discount Code: EP20

SCANTIFIX

Use Discount Code: Exploringpeptides

Canada

BIOSLAB

Use Discount Code: EP10

Europe

DNLABResearch

Use Discount Code: EP15

Australia

LVLUPHEALTH

References

[1] Ng, F. M., Sun, J., Sharma, L., Libinaka, R., Jiang, W. J., & Gianello, R. (2000). Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone. Hormone research, 53(6), 274–278. https://doi.org/10.1159/000053183

[2] Moré, M. I., & Kenley, D. (2014). Safety and metabolism of AOD9604, a novel nutraceutical ingredient for improved metabolic health. Journal of Endocrinology and Metabolism. https://doi.org/10.14740/jem213w

[3] Heffernan, M., Summers, R. J., Thorburn, A., Ogru, E., Gianello, R., Jiang, W.-J., & Ng, F. M. (2001). The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and β3-AR knock-out mice. Endocrinology, 142(12), 5182–5189. https://doi.org/10.1210/endo.142.12.8522

[4] Kwon DR, Park GY. (2015). Effect of Intra-articular Injection of AOD9604 with or without Hyaluronic Acid in Rabbit Osteoarthritis Model. Ann Clin Lab Sci. 2015 Summer;45(4):426-32. PMID: 26275694.

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