HGH Fragment 176-191: Evidence & Dosing Guide

HGH Fragment 176-191 at a glance

What it is

Synthetic 16-mer matching residues 176-191 of the 191-amino-acid human growth hormone molecule. Sequence H-Phe-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe-OH; commonly listed as CAS 66004-57-7. The commonly quoted C78H123N23O22S2 / ~1799.1 Da describes the cyclized (Cys182-Cys189 disulfide) form; the reduced linear form is C78H125N23O22S2 / ~1801.1 Da.

Researched for

Effects on lipid metabolism independent of the growth hormone receptor. The antilipogenic finding routinely attributed to this compound was actually generated on hGH 177-191, a 15-residue peptide contained within this sequence; in that work the effect was suppression of new fat synthesis, with no significant lipolytic activity detected.

Commonly reported range

250-500 mcg per injection in community settings; 250 mcg is the near-universal reported starting point. Reported daily totals cluster at ~500 mcg, with aggressive protocols reported up to ~1 mg/day. No validated human dosing exists.

Route reported

Subcutaneous injection after reconstitution of lyophilized powder with bacteriostatic water. No oral bioavailability data exists for this fragment specifically, and oral bioavailability of peptides this size is generally low. Intranasal and transdermal products are sold with no bioavailability data for this peptide.

Reported frequency

Most commonly twice daily (on waking and pre-bed), typically fasted, rationalized by a very short assumed half-life. Reported cycles cluster at 8-12 weeks.

Evidence status

Animal and ex-vivo work on closely related peptides only. No metabolic study of the intact 176-191 sequence has been published — the single identifiable published study using this exact sequence is an in-vitro oncology nanoparticle paper unrelated to fat metabolism — and no controlled human trial of this molecule exists. The human clinical record belongs to AOD-9604, a closely related but distinct peptide whose pivotal Phase 2b trial failed on efficacy and whose development was terminated in 2007.

Regulatory status

Not approved by FDA for any indication, human or veterinary, and not approved as a drug in any major regulated market. It is not eligible for lawful compounding under section 503A either: that section permits compounding from a bulk drug substance only where the substance has an applicable USP or NF monograph, is a component of an FDA-approved drug, or appears on FDA's 503A bulk drug substances list, and this fragment satisfies none of the three. US policy on peptide compounding has been revised repeatedly, and the current position is the one set out in FDA's own published guidance rather than in any summary of it. Sold as a research chemical, not for human consumption.

WADA status

Prohibited at all times, in and out of competition, and named explicitly. WADA's Prohibited List names hGH 176-191 by name, alongside AOD-9604, as an example of a prohibited growth hormone fragment within its section covering growth hormone, its fragments and releasing factors. The current edition of the List published by WADA is the governing source.

Reported ranges from research/community — examples, not recommendations.

What it is / mechanism

HGH Fragment 176-191 is the native C-terminal tail of human growth hormone: the last sixteen residues of the 191-amino-acid hormone, reproduced exactly, including the native Cys182 and Cys189 pair. Whether that pair is actually cyclized into a disulfide bridge in any given vial depends entirely on the manufacturer, and this is a real and under-discussed product-identity variable in the gray market. It is also visible in the numbers vendors print: the widely quoted formula C78H123N23O22S2 and mass of ~1799.1 Da describe the cyclized form. The reduced, linear form is C78H125N23O22S2 at ~1801.1 Da, the two hydrogens being exactly what disulfide formation removes. A catalogue page that quotes the cyclized mass has implicitly made a structural claim about its material, and two vials labeled identically can be structurally different molecules. The rationale for isolating this region is sound and dates to work at Monash University in the late 1970s: the growth hormone molecule appears to be functionally modular, and a set of metabolic activities associated with the C-terminal domain can be partially reproduced by short synthetic peptides drawn from it. One structural point in the popular account of this needs correcting, because it is stated backwards almost everywhere, including on vendor pages that otherwise get the chemistry right. The receptor-binding surface of hGH is not confined to the N-terminal and central regions. Alanine-scanning mutagenesis of the hGH-receptor interface (Cunningham and Wells, Science 1989) established that site 1 — the high-affinity receptor epitope — is dominated by helix 4, the C-terminal helix, with Phe176, Arg178 and Cys182 among the residues whose substitution measurably reduces binding. Those residues sit inside the 176-191 span. So the reason an isolated 16-mer does not behave like growth hormone at the receptor is not that receptor binding lives somewhere else in the sequence. It is that site 1 is a discontinuous, conformational epitope assembled from helix 4 together with helix 1 and the connecting loop, and a short unfolded peptide stripped of the four-helix bundle cannot reconstitute it. The observation that the fragment is not reported to raise IGF-1 is consistent with that, and it remains the part of the marketing story that survives scrutiny — but the correct explanation is loss of tertiary context, not a misdescription of where the epitope lies. The rest of the story is considerably weaker than vendor pages suggest. The near-universal marketed mechanism reads roughly as follows: the fragment binds adipocytes, stimulates lipolysis via hormone-sensitive lipase, inhibits lipogenesis, and upregulates beta-3 adrenergic receptor expression, all without GH-receptor engagement. There are two problems with this. First, the primary finding usually cited in support reports the opposite of the headline claim. Wu Z and Ng FM, "Antilipogenic action of synthetic C-terminal sequence 177-191 of human growth hormone" (Biochem Mol Biol Int 1993;30(1):187-96), examined epididymal fat pads from peptide-treated rats and reported antilipogenic activity identical to that of the intact hGH molecule, with no significant lipolytic effect as determined by the rate of glycerol release. The authors' conclusion was that growth hormone's main physiological effect in lipid metabolism is at the level of lipogenesis. Second, and this is a correction to how that paper is cited nearly everywhere: Wu and Ng studied hGH 177-191, a fifteen-residue peptide, not the sixteen-residue 176-191 fragment. The abstract names the sequence explicitly. That relationship is genuinely closer than the one between 176-191 and AOD-9604 — the 15-mer is wholly contained within 176-191, and the difference is the presence of the native Phe176 at the N-terminus rather than a non-native substitution — but by the standard this guide applies to every other citation, it is still extrapolation across a one-residue difference and has to be labeled as such. The accurate statement is this: the 177-191 core shared by all three molecules (177-191 itself, 176-191, and AOD-9604) showed antilipogenic but not lipolytic activity in rodent fat tissue in that 1993 work, and no published study has reported lipolytic activity for the intact 176-191 sequence. English-language Wikipedia's article on the fragment makes the same observation, describing the compound as one that "has erroneously been presented as a lipolytic peptide fragment" on the basis of extrapolation from AOD-9604 clinical data. That is tertiary commentary rather than evidence, and it is cited here as such — but it is a fair summary of the citation record. The beta-3 adrenergic mechanism has a similar provenance problem, compounded by a second layer of distortion. It originates in Heffernan MA et al., Endocrinology 2001;142(12):5182-9 — a study that used AOD9604, not the unmodified fragment. In beta-3-adrenergic-receptor knockout mice, neither hGH nor AOD9604 produced the weight-loss and lipolytic-sensitivity changes seen in wild-type controls. But the authors' actual conclusion was that the lipolytic actions are not mediated directly through the beta-3 receptor; rather, both compounds increase beta-3 receptor expression, which may secondarily raise lipolytic sensitivity. "Increases receptor expression in mice" is a materially different claim from "is a beta-3 agonist," and the peptide market has consistently collapsed the two while also transplanting the finding onto a molecule that was not in the study. A defensible mechanistic summary, then, is narrow. The C-terminal region of human growth hormone carries a lipid-metabolic domain that, in rodent and ex-vivo work on the 177-191 core, appears to suppress new fat synthesis, and an isolated 16-mer from this region cannot reconstitute the conformational receptor epitope. The absence of an IGF-1 rise belongs in that summary only with a caveat attached: the 1993 antilipogenic work measured lipogenesis in excised fat pads and did not assay IGF-1 at all. The fragment is not reported to raise IGF-1 chiefly because it has no measurable GH-receptor activity and because the AOD-9604 human program found no consistent IGF-1 effect — an inference from GH-axis reasoning and from data on a related molecule, not a measurement on this one. Everything beyond that — direct lipolysis, beta-3 agonism, cartilage repair, site-specific fat loss — either rests on AOD-9604 data transferred to this molecule without direct evidence, or has no experimental basis at all. Worth adding for completeness, because it is the one part of this region's own literature that vendors never cite: the foundational Monash papers on C-terminal hGH fragments were not about fat loss but about glucose. Ng FM and Bornstein J (Am J Physiol 1978) reported that hGH 177-191 produced a short-lived rise in blood glucose and a more sustained rise in plasma insulin, and that peptides containing residues 178-191 significantly reduced insulin sensitivity on intravenous insulin tolerance testing. Ma GY et al. (Biochim Biophys Acta 1982) traced a mechanism: transient increases in blood glucose and lactate, a decreased glycogen synthase activity ratio in muscle, adipose and liver, and decreased pyruvate dehydrogenase in muscle and adipose. The literature on this exact region of the hormone is titled around its "hyperglycaemic" and "diabetogenic" action.

Researched effects

There is no controlled human efficacy data on HGH Fragment 176-191, so "reported effects" here means exactly that: what is described in community settings, plus what was observed in rodents given related C-terminal peptides decades ago. The most commonly reported subjective outcome is gradual reduction in body fat over an 8-12 week run, particularly when combined with a caloric deficit. Also commonly reported is an absence of the appetite suppression, nausea and gastrointestinal effects that characterize incretin-based agents, and an absence of the joint discomfort, carpal tunnel symptoms and pronounced fluid retention associated with exogenous growth hormone or high-dose secretagogues. That last point needs stating precisely, because it is frequently overstated into a claim this guide's own side-effect section contradicts. The GH-type fluid-retention syndrome — sustained edema, carpal tunnel compression, joint stiffness — is IGF-1- and GH-mediated, and would not be expected from a compound that does not raise either. That is a mechanistic expectation, not an observed absence. Community reports on this fragment do include transient puffiness or mild water retention, described as short-lived and low-grade rather than the sustained edema seen with growth hormone. The consistent reading of both observations is that the GH-type retention syndrome is not what community sources describe for this peptide, while brief mild puffiness sometimes is, and neither observation comes from a controlled study. What is much less credible is the magnitude of the fat-loss claims attached to this compound. The specific numbers circulating on vendor sites come from a Phase 2 trial of AOD-9604 run by Metabolic Pharmaceuticals in Australia in the mid-2000s: a 12-week study, reported as five-site and enrolling roughly 300 obese patients, in which the drug was taken orally once daily across a placebo arm and reported dose arms of 1, 5, 10, 20 and 30 mg. The figure quoted online for the 1 mg arm is an average loss of roughly 2.6 kg against roughly 0.8 kg on placebo, with some accounts giving 2.8 kg instead; it traces to company disclosure from late 2004 rather than to a peer-reviewed publication, and is best read as a press-release number. Three things are almost always omitted alongside it. It was a different molecule. It was an oral trial, which makes it a strange citation for an injectable protocol. And it is not where the program ended: the larger, longer Phase 2b — reported at roughly 500 obese subjects over 24 weeks, again oral, again against placebo — failed to separate from placebo on its primary endpoint at any dose, and development was terminated in 2007. Quoting the 2004-era figure for a compound that never had a human trial of its own, while omitting the terminal outcome of the program that generated the figure, is the single most common form of misrepresentation on this compound. A further category of claim should be dismissed outright. "Cartilage regeneration" and joint-repair benefits are routinely attached to Fragment 176-191; the sole source is Kwon DR and Park GY's study of intra-articular AOD9604 in a rabbit osteoarthritis model (Ann Clin Lab Sci, 2015) — rabbit data, different peptide, intra-articular route. Site-specific or "spot" fat reduction from injecting into abdominal subcutaneous fat has no supporting evidence for this peptide or any other; subcutaneous injection delivers peptide into systemic circulation, and localized fat mobilization from the injection depot is not a demonstrated phenomenon. Finally, the frequently repeated line that this fragment "does not affect blood sugar" is drawn from AOD-9604's human safety record and sits uncomfortably beside the 1978-1982 animal work on this region of the hormone, which reported transient hyperglycemia and reduced insulin sensitivity. The honest position is that nobody knows what this molecule does to glucose handling in humans, because nobody has measured it.

Dosage — reported ranges (overview)

There is no clinically validated dosing protocol for HGH Fragment 176-191, because there has never been a human trial from which to derive one. Every figure below is a community and forum convention reported in bodybuilding and peptide-user settings, presented descriptively as a record of what circulates elsewhere. None of it is a recommendation, and none of it has been through dose-ranging, safety, or pharmacokinetic study in humans. The most commonly reported unit dose is 250 mcg subcutaneously, which functions as the near-universal reported starting point. The dominant convention is 250 mcg twice daily — typically on waking and again before bed — for roughly 500 mcg per day. More aggressive cutting protocols are reported at 500 mcg per injection and daily totals approaching 1 mg. Reported cycle lengths cluster at 8-12 weeks, usually framed around a caloric deficit rather than as a standalone intervention. Two administration conventions dominate, and both deserve a critical note. The first is fasted dosing, rationalized on the grounds that elevated insulin and circulating substrate blunt fat mobilization; this is mechanistic reasoning extrapolated from general metabolic physiology, not a finding from any trial of this peptide. The second is dose splitting, justified by an assumed very short half-life; that logic is internally coherent but rests on a half-life figure that has never been measured for this molecule. The practical hazard specific to this compound is arithmetic rather than pharmacological. It is sold almost exclusively as 2 mg, 5 mg, and 10 mg lyophilized vials, while reported doses sit at 250-500 mcg — meaning a single vial contains between four and forty reported doses, and the drawn volume for a given dose changes by a factor of five between the smallest and largest vial at identical reconstitution volume. A 5 mg vial in 2 mL yields 2,500 mcg/mL, so 250 mcg is 10 units on a U-100 insulin syringe; a 10 mg vial in the same 2 mL yields 5,000 mcg/mL, and the same 250 mcg is 5 units. Misreading vial size produces a clean 2x error in either direction, and because both vials look identical once reconstituted, the error is invisible after the fact. Labeling reconstituted vials with the mass loaded, the water added, and the resulting mcg/mL — not just the compound name — is the standard safeguard described in research handling practice.

The full step-by-step protocol examples, titration schedule, and a printable protocol sheet with a dosing and injection log are included in the paid Protocol Playbook for this guide.

Reconstitution — bac-water math

Reconstitution is straightforward arithmetic: concentration equals the vial's total peptide mass divided by the volume of bacteriostatic water added. Once concentration in mcg per mL is known, the volume for any dose is dose divided by concentration, and insulin-syringe units are simply mL x 100 (a U-100 syringe marks 100 units per 1 mL, so 1 unit = 0.01 mL). The table below works this through for the vial sizes this compound is actually sold in, at the two most commonly reported unit doses. Reconstitution technique is commonly described in research and community settings as directing the bacteriostatic water slowly down the inside wall of the vial rather than jetting it onto the lyophilized cake, followed by gentle swirling until the cake fully dissolves; shaking is avoided because peptides are sensitive to shear and foaming. Powder that does not fully clear, or a solution that is cloudy or contains particulate, is generally treated as a product-quality signal rather than something to work with. The drawn volume changes sharply between the 5 mg and 10 mg rows at identical water volume, and that difference is where dosing errors on this compound overwhelmingly occur.

This is concentration math, not a dose recommendation.

Injection / administration basics

In research and community protocols this peptide is described as administered subcutaneously with a U-100 insulin syringe, most often 29-31 gauge and 5/16 to 1/2 inch, into loose subcutaneous tissue of the abdomen (avoiding a roughly two-inch radius around the navel), the flank, or the outer thigh. The aseptic practice reported in those settings includes: swabbing the vial stopper and the injection site with 70% isopropyl alcohol and allowing both to air-dry; using a fresh sterile syringe for every administration; lifting a fold of subcutaneous tissue; inserting at 45-90 degrees depending on tissue depth; injecting slowly; and rotating sites between administrations to limit local tissue changes. Aspiration is not standard practice for subcutaneous injection of small volumes. Sharps disposal is described as going into a proper sharps container rather than household waste. Two administration points are specific to this compound. First, the abdominal injection site is frequently framed as producing localized or "spot" fat reduction. It does not. Subcutaneous injection places the peptide into systemic circulation, and there is no evidence for site-specific fat loss with this or any other peptide; the abdomen is a convenient site with reliable subcutaneous depth, and that is the whole of its advantage. Second, the fasted-dosing convention means reported injections commonly occur on waking and before bed. Lightheadedness or transient fatigue reported after fasted administration is more plausibly a function of fasting itself than of the peptide, but reports of it do cluster around those two fasted administration windows. Other routes deserve a careful rather than a sweeping assessment, because sweeping claims are easy to make here and hard to support. There is no oral bioavailability data for HGH Fragment 176-191 specifically, and oral bioavailability of an unprotected 16-mer with a free N-terminus is expected to be low, since gastrointestinal proteases degrade peptides of this class readily. But "not orally bioavailable" is too strong a statement, and it is contradicted by the very data most often quoted for this compound: the AOD-9604 Phase 2 and Phase 2b programs both administered the peptide orally, once daily, and an earlier study of oral administration of a related C-terminal hGH fragment (AOD9401) in obese mice reported measurable effects on adipose lipogenic and lipolytic activity (Am J Physiol Endocrinol Metab 2000;279(3):E501). Whatever those results mean, they were obtained by the oral route. The defensible position is that oral activity for this class is not zero, has never been characterized for the 176-191 sequence, and is not a basis for using oral products marketed under this name. Intranasal and topical/transdermal preparations are also sold, with no meaningful bioavailability data for this peptide by either route, and a molecule of roughly 1,800 Da does not cross intact skin in appreciable quantity without a delivery technology these products do not have.

Half-life & frequency rationale

No published human pharmacokinetic study of HGH Fragment 176-191 exists, by any route. Any specific half-life figure attributed to this molecule is an extrapolation, and confident numbers on vendor pages are best read as inference dressed up as measurement. What is actually known comes from AOD-9604 and from general peptide chemistry. Plasma half-life for this class is very short — on the order of minutes. Reported AOD-9604 values include roughly 3 minutes plasma half-life after intravenous administration in pigs, with other sources citing an elimination half-life in the region of 30-38 minutes; degradation is described as proceeding by sequential removal of N-terminal amino acids, which is exactly the vulnerability a free, unprotected N-terminus creates. Community sources commonly quote 15-30 minutes for Fragment 176-191, which is entirely plausible for an unprotected linear 16-mer with no half-life-extending modification, but it is not a measured value for this peptide. Subcutaneous administration adds an absorption phase that lengthens the apparent duration somewhat relative to intravenous data, without changing the underlying picture of rapid clearance. One nuance is worth stating so the short half-life is not misread as short duration of effect. In the AOD9604 animal work, effects on body weight and fat metabolism persisted for hours to days despite rapid plasma clearance — a common pattern for peptides that act by altering gene or receptor expression rather than through sustained receptor occupancy. If the mechanism really does run through changes in adipocyte enzyme and receptor expression, then plasma residence time and biological duration are only loosely coupled. That said, the very short assumed plasma half-life is the stated rationale for the twice-daily community dosing convention, and it is fair to note that this rationale and the persistence-of-effect observation pull in opposite directions. Neither has been tested in humans for this molecule.

Stacking — overview

Stacking discussion for this compound is unusually detached from evidence, because there is no controlled human data on the peptide alone, let alone in combination. Nothing below has been studied as a combination in humans; these are pairings commonly discussed in research and community settings, described together with the reasoning behind them and the limits of that reasoning. Combining compounds compounds unknowns — additive risk, unpredictable interactions, and no ability to attribute either an effect or an adverse event to any one input. The most conceptually interesting pairing is with growth hormone secretagogues, and it is worth understanding why it is conceptually strange. CJC-1295, ipamorelin, sermorelin, mod-GRF 1-29 and the GHRPs all work upstream, increasing endogenous GH release and, downstream of that, IGF-1. Fragment 176-191 is the opposite arrangement: a downstream piece of the GH molecule whose entire selling point is that it does not raise GH or IGF-1. Running both means deliberately restoring the IGF-1 axis the fragment was selected to avoid, which is a coherent goal if recovery and body composition are both objectives, but it dissolves the main rationale for choosing the fragment in the first place. In any such combination, the secretagogue is the component with actual human pharmacodynamic data behind it. The pairing with genuine evidence on the other side is tesamorelin, and it is instructive as a contrast rather than a combination. Tesamorelin is a GHRH analogue that is FDA-approved (as Egrifta) for HIV-associated lipodystrophy, with human trial data showing visceral fat reduction — and it works by raising GH and IGF-1, the exact opposite design philosophy. Where visceral adiposity is the subject and the evidence base matters, tesamorelin and the fragment are not in the same tier. Similarly, the incretin and amylin agents — semaglutide, tirzepatide, retatrutide, cagrilintide — operate through a completely different mechanism with large randomized human trials behind them, and adding a fragment with no human data to a GLP-1 protocol adds unknowns without adding demonstrated effect.

For how combinations are grouped by research context, the named blends, and why a pre-mixed blend vial cannot be calculated from its total milligrams, see the peptide stacks guide.

Storage & handling

• Lyophilized (unreconstituted) vials are described as stable refrigerated at 2-8 °C, and are commonly reported to tolerate room temperature for short periods during shipping. For long-term holding, -20 °C is standard practice for research peptides. Storage in original packaging and protected from light is standard handling practice; the light- and oxidation-sensitive feature of this particular sequence is the Cys182/Cys189 thiol-disulfide pair, which can oxidize, scramble, or reduce depending on conditions. The peptide contains no tryptophan, no tyrosine and no methionine, the residues that usually drive peptide photodegradation, so the phenylalanine residues are not the concern here — the cysteines are.
• Once reconstituted with bacteriostatic water, refrigeration at 2-8 °C and use within roughly 28 days is the standard window — the same in-use period that the 0.9% benzyl alcohol preservative in bacteriostatic water is labeled to support after first puncture under USP and manufacturer labeling. Reconstitution with plain sterile water instead provides no preservative protection at all, which is why that practice is described as reducing the practical window to about 24 hours refrigerated.
• Reconstituted solutions are not frozen in standard handling practice. Freeze-thaw cycles cause peptide aggregation and loss of potency, and for this sequence specifically can disrupt the Cys182-Cys189 disulfide arrangement where it is present. A reconstituted vial that has frozen accidentally at the back of a refrigerator is generally treated as compromised.
• Labeling every reconstituted vial with the mass loaded, the water volume added, the resulting mcg/mL, and the reconstitution date is described as essential rather than optional for this compound: 5 mg and 10 mg vials look identical once dissolved, and the drawn volume for the same dose differs by exactly 2x between them. Most reported dosing errors on this peptide originate here.
• Shaking is avoided; gentle swirling until the cake fully dissolves is the described method. Inspection before each draw is standard practice — the solution is expected to be clear and free of particulate. Cloudiness, visible precipitate, or a cake that will not dissolve are treated as product-quality signals and grounds to discard rather than to proceed.

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