HGH Fragment 176-191
The unmodified lipolytic C-terminal fragment of human growth hormone and the parent of AOD-9604, sold heavily for fat loss on the strength of mouse studies and very little else.
Also known as Frag 176-191, GH fragment, Lipolytic fragment, hGH 176-191
Animal data only — Rodent or other animal studies. Dose translation to humans is genuinely uncertain.
The lipolytic activity of the GH C-terminal region is well established in rodent adipocytes and in obese mouse models. There is no controlled human trial of the unmodified 176-191 fragment, and the closest analogue that was tested in humans - AOD-9604 - failed its obesity endpoint. Treat the fat-loss marketing accordingly.
How it works
This is residues 176 to 191 of the 191-amino-acid human growth hormone molecule, the region identified in the 1980s as carrying GH's lipolytic activity independently of its growth-promoting and diabetogenic activity. In rodents it increases fat oxidation and reduces adipose mass without changing IGF-1 or glucose tolerance. Crucially, the fragment is not a secretagogue at all - it does not raise GH, and it does not act at GHS-R1a or the GHRH receptor - so its presence in this class is historical rather than mechanistic. It is less stable than AOD-9604, which is exactly why the tyrosine-extended version was developed, and no human trial has ever demonstrated meaningful fat loss from the fragment itself.
Targets: Adipocyte lipolytic pathways, Beta-3 adrenergic signalling, Lipogenic enzymes
Dosing
| Protocol | Dose | Frequency | Route |
|---|---|---|---|
| Common grey-market protocolFasted on waking and, if split, before bed - the rationale is to avoid insulin blunting lipolysis. | 250 mcg – 500 mcg | once or twice daily | subcutaneous |
| Pre-cardio single doseThirty minutes before fasted cardio. | 250 mcg – 500 mcg | once daily | subcutaneous |
- · 500 mcg per day total is the most commonly quoted figure. There is no dose-finding study behind it.
- · Popular timing convention rather than an evidence-based one.
Cycling
Usually run 8 to 12 weeks alongside a deficit. Since there is no evidence of receptor desensitisation or accumulation, cycle length is essentially arbitrary.
Pharmacology
- Half-life
- Short - roughly 30 minutes or less, and not formally characterised in humans.
- Onset
- No reliable acute effect; claimed changes over 8 to 12 weeks are not supported by controlled human data.
- Routes
- subcutaneous
- Molecule
- Synthetic 16-residue C-terminal fragment of human growth hormone
- Sequence length
- 16 amino acids
- Molecular weight
- 1817.1 Da
Handling
- Diluent
- Bacteriostatic water
- Typical mix
- 2 mL
- Vial sizes
- 2, 5 mg
- Lyophilised
- Refrigerate; freeze for long-term storage.
- Reconstituted
- Refrigerated, use within about 21 to 30 days.
- Light sensitive
- Yes — keep it out of the light
Mixing
A 5 mg vial in 2 mL gives 2500 mcg/mL; 10 units on a U-100 syringe is 250 mcg.
Side effects
- very commonNothing perceptible at all— The most common user report, which is consistent with the absent human efficacy data.
- commonInjection-site redness or irritation
- uncommonHeadache
- uncommonTransient flushing
Do not use if
- Pregnancy and breastfeeding.
- Known hypersensitivity.
Combining it
- redundantaod-9604 — Same fragment, one with a stabilising tyrosine. Pick one.
- cautioncjc-1295-no-dac — Frequently sold as a bundle. The GHRH arm does the work; the fragment is filler.
What to monitor
- · Body composition and waist measurement.
- · No specific bloodwork is indicated, since the fragment does not move IGF-1 or glucose.
Legal status
Not approved for human use anywhere; sold as a research chemical. Prohibited in sport under WADA S2.
References
- Ng and Bornstein, identification of the lipolytic domain in the hGH C-terminus (preclinical)
- Heffernan et al. 2001, lipolytic activity of the hGH 177-191 fragment in mice (preclinical)
Mechanism in depth
This entry contains the single most practically useful correction in this class, so it is worth stating plainly. The mature human growth hormone chain was retrieved directly from UniProt P01241 and ends ...MDKVETFLRIVQCRSVEGSCGF. Counting back sixteen residues, hGH(176-191) is FLRIVQCRSVEGSCGF - it begins with phenylalanine. The sequence that virtually every vendor prints on a vial labelled 'HGH Fragment 176-191', YLRIVQCRSVEGSCGF beginning with tyrosine, is not hGH(176-191) at all. It is AOD-9604: hGH(177-191) with an N-terminal tyrosine bolted on. So a large fraction of what is sold as the unmodified fragment is either AOD-9604 under a different name, or something synthesised to a sequence that does not correspond to the label. Mechanistically, the C-terminal region of GH was identified in the 1980s as carrying lipolytic activity separable from GH's growth-promoting and diabetogenic actions, and in rodents this fragment increases fat oxidation and reduces adipose mass without changing IGF-1 or glucose tolerance. It is not a secretagogue. It does not raise GH, it does not act at GHS-R1a or the GHRH receptor, and its presence in this class is a historical accident of it being a GH-derived molecule. Everything in the AOD-9604 entry about the beta-3 adrenergic dependence and the failed human translation applies here with less evidence behind it, because the unmodified fragment has never been through a controlled human trial at all - its closest tested relative failed.
What usually goes wrong
You almost certainly do not have what the label says. Given that the sequence sold as 176-191 is usually AOD-9604's sequence, the most likely outcomes are that you have AOD-9604 at a markup, or a peptide synthesised to a sequence nobody has verified. Beyond that, the failure mode is the same as AOD-9604's but with less evidence behind it: no perceptible effect, no marker to track, twelve weeks of injections, and a body-composition change entirely attributable to the diet you were running anyway. The most common user report in the Core record - 'nothing perceptible at all' - is consistent with the pharmacology. The pre-cardio timing convention, the fasted-dosing rationale about insulin blunting lipolysis, and the 250 to 500 mcg dose range are all conventions rather than findings.
Bloodwork worth running
| Marker | When | Why it matters |
|---|---|---|
| Body composition and waist circumference | Baseline and 12 weeks. | The only outcome the compound claims, and the only one worth measuring.Act if: No change beyond what the diet explains means it is doing nothing, which is the outcome the evidence predicts. |
| IGF-1 | Optional, baseline and 12 weeks. | Purely as a product identity check. This fragment should not move IGF-1 by a single point.Act if: Any rise means the vial contains something with GH-axis activity, which is worth knowing. |
Pharmacokinetics
- Crosses blood-brain barrier
- no
- Metabolism
- Peptidase hydrolysis. The fragment is less stable than AOD-9604, which is the documented reason the tyrosine-extended version was made.
- Elimination
- Not characterised.
Receptor targets
- Adipocyte lipolytic pathways — No defined receptor. The molecular target of the GH C-terminal lipolytic domain has never been identified.
Increased fat oxidation and reduced adipose mass in rodents. Not demonstrated in humans.
- Beta-3 adrenergic signalling (indirect) — Not a direct ligand
Inferred from the AOD-9604 knockout-mouse work rather than demonstrated for this fragment specifically.
- Growth hormone receptor — No meaningful binding
Absent by design. IGF-1 and glucose tolerance unchanged.
- GHS-R1a and GHRH receptor — None
No activity. This compound is not a growth hormone secretagogue despite its placement in this class and the way it is marketed.
What to expect, and when
No reliable acute effect and no established onset. Claimed changes over eight to twelve weeks are not supported by any controlled human data on this fragment.
Stacking and comparisons
Frequently bundled with a GHRH analogue or a GHRP as a 'fat loss stack', where the secretagogue arm does whatever work gets done. It is redundant with AOD-9604, which is the same molecule plus a tyrosine and minus a labelling problem. It does not interact with anything because it does not engage any characterised receptor system - which makes it safe to combine and pointless to combine.
Against AOD-9604: AOD-9604 is the same molecule with a stabilising tyrosine and an actual human trial behind it. There is no scenario where the unmodified fragment is the better purchase. Against tesamorelin: tesamorelin is the compound with a real, imaging-confirmed regional fat effect and an FDA approval; this fragment is the cheap substitute that does not substitute. Against a GLP-1 agonist: not in the same category of evidence or effect. Against doing nothing: the honest comparison, and the one the evidence supports.
Rough cost
$35–$90/month. Approximate grey-market pricing. A 5 mg vial typically runs 30 to 60 USD; at 500 mcg daily that is about 15 mg a month, so two to three vials. You are paying AOD-9604 prices for a less stable and probably mislabelled version of the same thing. Figures are observed and approximate.
Genuinely uncertain
- The single biggest uncertainty is what is actually in the vial. The sequence marketed as hGH(176-191) is AOD-9604's sequence, so product identity is unresolvable without independent analysis.
- No human trial of the unmodified fragment has ever been conducted - no efficacy, no pharmacokinetics, no safety.
- The molecular weight of 1817.1 in the Core record does not match the calculated mass of the verified FLRIVQCRSVEGSCGF sequence, which comes out near 1801 Da for the reduced free acid. 1817 is closer to the tyrosine-containing AOD-9604 sequence, which is consistent with the labelling confusion described above.
- The molecular target of the GH C-terminal lipolytic domain has never been identified, so 'mechanism' here means an observed rodent effect rather than a receptor.
- The 30-minute half-life is an assumption from peptide size.
- The dosing conventions - 250 to 500 mcg, fasted, pre-cardio - have no experimental basis whatsoever.
Papers
- UniProtKB P01241, somatotropin (human growth hormone) UniProt Knowledgebase
Primary sequence source, retrieved directly. Establishes that mature hGH ends ...VETFLRIVQCRSVEGSCGF and therefore that residue 176 is phenylalanine, which is how the labelling discrepancy is resolved.
- Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment Heffernan MA, Thorburn AW, Fam B, et al., International Journal of Obesity and Related Metabolic Disorders, 2001 · PMID 11673763
The rodent evidence for the lipolytic activity of the GH C-terminal fragment. Note that the tested molecule was the modified fragment.
- 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 Heffernan M, Summers RJ, Thorburn A, et al., Endocrinology, 2001 · PMID 11713213
The mechanistic basis, and the reason to expect poor human translation given how much less beta-3-dependent human adipose lipolysis is.
- Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone Ng FM, Sun J, Sharma L, Libinaka R, Jiang WJ, Gianello R, Hormone Research, 2000 · PMID 11146367
Ng's group identified the lipolytic domain; this is the closest thing to a primary source for the region's activity.