HGH Fragment 176-191 5mg

Fragment 176-191 is a synthetic peptide derived from amino acids 176-191 of human growth hormone (hGH). As one of several synthetic C-terminal fragments of hGH studied in rodent models, it has demonstrated potential benefits such as lowering blood sugar without increasing IGF-1 or affecting insulin sensitivity—side effects commonly associated with hGH therapy【1】.

While research specific to fragment 176-191 is limited, studies on the structurally similar peptide AOD9604 (fragment 177-191) offer insights into its potential mechanism of action, benefits, and safety profile【2】.

What Does Fragment 176-191 Do?

The precise mechanism of action of fragment 176-191 remains unclear. However, its effects are believed to parallel those of AOD9604, a low-affinity agonist of the growth hormone (GH) receptor. AOD9604 retains certain GH functions, such as promoting cartilage metabolism and fat loss, without causing the pro-tumor or pro-diabetic effects associated with traditional GH injections【3】.

As a GH receptor agonist, AOD9604 binds to GH receptors to:

• Induce fat metabolism.
• Increase energy consumption and fat oxidation.
• Stimulate the formation of myoblasts (muscle progenitor cells).

Fragment 176-191 is believed to function similarly, supporting its reputation as the “lipolytic fragment” of HGH due to its fat-burning effects observed in preclinical studies【1】.

Fragment 176-191: Benefits and Clinical Insights

1. Fat-Burning Effects

Fragment 176-191 has demonstrated significant fat-reduction effects in rodent models:

• Rodent Study on AOD9604 (2001):
  AOD9604 administration reduced body weight and fat in obese mice over 14 days. The peptide increased beta-3 adrenergic receptor (ADRB3) production, essential for fat metabolism. Notably, this effect was absent in lean mice and mice genetically lacking ADRB3【6】.

These findings suggest fragment 176-191 may target a secondary pathway for fat metabolism that becomes less active as body weight normalizes.

2. Potential in Diabetes Management

Fragment 176-191 shows promise for managing prediabetes and type 2 diabetes:

• Animal Research:
  Studies on various hGH fragments (172-191, 176-191, 177-191, etc.) found the hypoglycemic effect primarily linked to the C-terminal region. Among the fragments tested, fragment 176-191 was the most effective at reducing blood sugar. Secondary benefits included sustained increases in plasma insulin and reduced insulin sensitivity【1】.

3. Cartilage Regeneration

Preliminary evidence suggests fragment 176-191 may promote cartilage repair:

• Rabbit Study on AOD9604 (2015):
  In a model of knee osteoarthritis, AOD9604 combined with hyaluronic acid (HA) enhanced cartilage regeneration. The combination outperformed either AOD9604 or HA alone【7】.

These findings indicate fragment 176-191 may offer similar benefits, potentially aiding in advanced osteoarthritis treatments or reducing the need for surgery.

Side Effects of Fragment 176-191

No clinical studies have been conducted specifically on fragment 176-191, and its side effects remain largely unknown. However, data from AOD9604 trials provide valuable context:

• General Safety:
  AOD9604 trials reported no significant side effects typically associated with hGH, such as insulin resistance, hypertension, or increased IGF-1 levels.
• Reported Adverse Events (AEs):
  In a dose-escalation study of AOD9604 in healthy male subjects, 12 out of 15 participants reported mild AEs, including:

• • Headache: 6 occurrences
  • Fatigue: 4 occurrences
  • Hypoglycemia (unspecified): 3 occurrences
  • Dizziness: 3 occurrences
  • Additional single reports of lethargy, abdominal pain, sore throat, injection site reactions, and seasonal rhinitis【8】.

Overall, AOD9604 was well-tolerated at doses ranging from 25 µg to 400 µg/kg body weight. Researchers noted its safety profile was comparable to rhGH and placebo.

Conclusion

Fragment 176-191 is a promising peptide with potential applications in fat loss, diabetes management, and cartilage regeneration. While direct clinical evidence is limited, studies on the closely related AOD9604 offer compelling insights into its mechanism, benefits, and safety profile. Researchers are encouraged to further explore fragment 176-191 to unlock its full therapeutic potential.

References

1. Ng FM, Bornstein J. Hyperglycemic action of synthetic C-terminal fragments of human growth hormone. Am J Physiol. 1978 May;234(5):E521-6. doi: 10.1152/ajpendo.1978.234.5.E521. PMID: 645904.
2. Sekar, M., Okumu, F., van Osdol, W., Tamraz, W., Tung, D., & Sverdrup, F. (2009, June). SABER™ formulation for intra-articular delivery of recombinant human growth hormone. In 2009 AAPS National Biotechnology Conference. Poster# NBC-09-00476 (Vol. 166).
3. Matsuzaka S, Sato S, Miyauchi S. Estimation of joint fluid volume in the knee joint of rabbits by measuring the endogenous calcium concentration. Clin Exp Rheumatol. 2002 Jul-Aug;20(4):531-4. PMID: 12175108.
4. Dunn AR. Morphoangiogenesis: a unique action of growth hormone. Microvasc Res. 2002 May;63(3):295-303. doi: 10.1006/mvre.2002.2412. PMID: 11969306.
5. Mankin, H. J. (1971). dorfman H, Lippiello L and Zarins A: Biochemical and metabolic abnormalities in articular cartilage from osteo-arthritic human hips. II. correlation of morphology with biochemical and metabolic data. J Bone Joint Surg Am, 53, 523-537.
6. Heffernan M, Summers RJ, Thorburn A, Ogru E, Gianello R, Jiang WJ, Ng FM. The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and beta(3)-AR knock-out mice. Endocrinology. 2001 Dec;142(12):5182-9. doi: 10.1210/endo.142.12.8522. PMID: 11713213.
7. Kwon DR, Park GY. 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.
8. Stier, Heike et al. “Safety And Tolerability Of The Hexadecapeptide AOD9604 In Humans”. Jofem.Org, 2021, https://www.jofem.org/index.php/jofem/article/view/157.
9. Ng FM, Sun J, Sharma L, Libinaka R, Jiang WJ, Gianello R. Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone. Horm Res. 2000;53(6):274-8. doi: 10.1159/000053183. PMID: 11146367.
10. Heffernan MA, Thorburn AW, Fam B, Summers R, Conway-Campbell B, Waters MJ, Ng FM. Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment. Int J Obes Relat Metab Disord. 2001 Oct;25(10):1442-9. doi: 10.1038/sj.ijo.0801740. PMID: 11673763.