Hexarelin: The Response Fades, and the Community Dose Was Already Tested

The molecule, and the one standing next to it

Hexarelin is a synthetic chain of six amino acids, His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH2, PubChem CID 6918297, and an analogue of GHRP-6 differing by a single substitution at position two, where GHRP-6's D-tryptophan becomes D-2-methyl-tryptophan. Worth saying, because GHRP-6's evidence gets quoted as hexarelin's routinely. Its growth-hormone-releasing action runs through the ghrelin receptor, GHS-R1a (PMID 11988484).

What one dose does in a person

Massoud, Hindmarsh and Brook gave healthy adult males 0 to 1.0 mcg/kg into a vein and measured more than growth hormone: it plateaued at 140 mU/L, prolactin rose by up to 180 percent above baseline, and cortisol took a step up of about 40 percent at 0.5 mcg/kg (PMID 8954038). Not selective in humans, and measured in people rather than inferred from another species.

What sixteen weeks did to the response

Rahim, O'Neill and Shalet gave twelve healthy elderly people hexarelin at 1.5 mcg/kg of body weight, under the skin, twice daily, for 16 weeks, rechallenging them at intervals (PMID 9589671). At baseline the area under the growth hormone curve was 19.1 +/- 2.4 mcg/L.h. By week one it had already fallen to 13.1 +/- 2.3, about 31 percent gone before anything reached significance (PMID 10990150). Week 4 came in at 12.3 +/- 2.4 (P below 0.05) and week 16 at 10.5 +/- 1.8 (P below 0.01), a fall of roughly 45 percent. Four weeks after the last injection they were challenged again and the response had returned to 19.4 +/- 3.7, so the attenuation is partial and it reverses.

Now the part that decides the compound. Across those same 20 weeks serum IGF-1 and IGF binding protein-3 did not change significantly, P = 0.24 and P = 0.74, and total body fat, lean body mass and bone mineral density had not changed at week 16 either. The authors read the schedule's impact on the growth hormone and IGF-1 axis as minimal. So the response faded, and there was arguably nothing downstream for the fading to take away. Picture shouting an order through a serving hatch into a kitchen that never sends any food out. After a few weeks you shout less loudly. Dinner is the same either way.

Days do not produce this. Ghigo and colleagues ran two short courses in 1996, seven elderly subjects on intranasal hexarelin 1.25 mg (about 18 mcg/kg) three times daily for 8 days and seven elderly women on oral hexarelin 20 mg (about 300 mcg/kg) three times daily for 15 days, and neither blunted the response, moved prolactin or cortisol, or caused a side effect (PMID 8921821). Nor does a suppressed response mean the effect has gone: in two uncontrolled studies in short children, dosing intranasally for months, growth velocity rose anyway, in one of them with pituitary responsiveness partially suppressed (PMID 8766941, PMID 8548949).

The heart, and what was measured

Bisi and colleagues gave seven male volunteers either recombinant human growth hormone or hexarelin into a vein. Both raised growth hormone similarly and only hexarelin raised ejection fraction, 70.7 +/- 3.0 percent against 64.0 +/- 1.5 percent, pbelow 0.03 (PMID 10342360). Matching the hormone exposure and finding only the peptide moves the heart is what makes the effect independent of growth hormone; the same group found it again in growth-hormone-deficient men (PMID 10528131). The largest I found put 24 men with coronary artery disease on 2.0 mcg/kg into a vein during bypass surgery, with a prompt rise in ejection fraction from ten minutes and in cardiac output lasting up to 90 minutes, while growth hormone, GHRH and placebo did nothing (PMID 12144941).

Five human cardiac studies, every one a single acute dose into a vein, almost always 2.0 mcg/kg. I could find no repeat-dose human cardiac study and no human cardiac data at all by the subcutaneous route. The chronic version of the story is rats: Rossoni and colleagues gave 24-month-old male rats 80 mcg/kg subcutaneously twice daily for 21 days, after which recovery of left ventricular developed pressure following ischaemia was almost complete, 90 percent of pre-ischaemic values against 55 percent for growth hormone (PMID 9700988), roughly 53 times the 1.5 mcg/kg twice daily of the only long-term human study, before allometric adjustment.

CD36, and the direction it actually ran

Bodart and colleagues labelled rat cardiac membranes with a radioactive photoactivatable hexarelin derivative and purified an 84 kDa binding protein whose N-terminal sequence was identical to rat CD36, with the response absent in hearts from CD36-null mice and from spontaneously hypertensive rats deficient in CD36. The receptor story is real in its origin. What the sales pages leave out is the direction: in those perfused rat hearts hexarelin raised coronary perfusion pressure dose-dependently, which is vasoconstriction, and the paper closes by suggesting CD36 may mediate the coronary vasospasm of hypercholesterolaemia and atherosclerosis (PMID 11988484). The tidy anti-atherosclerotic results belong to EP-80317, a different compound, from the GHRP family but devoid of growth-hormone-releasing activity, and its mouse data is not hexarelin's (PMID 16123174, PMID 23880196). No human study connects hexarelin's cardiac effect to CD36.

Where the hundred micrograms comes from

Vendor and community sources vary. Roughly 100 mcg per subcutaneous injection circulates as entry level, two to three times daily for 200 to 300 mcg per day, though several call 200 mcg twice daily standard and some go higher, on cycles of about 6 to 8 weeks with a 4 to 8 week break framed explicitly as managing desensitisation. Convention, not evidence, and I could not establish any published derivation for the 100 mcg figure.

Converted to a per-injection amount, the trial dose lands somewhere unusual. Rahim's 1.5 mcg/kg subcutaneously twice daily works out at about 105 mcg per injection and 210 mcg per day for a 70 kg adult, or 120 mcg and 240 mcg per day at 80 kg, so the community number sits on a studied dose, by the same route, and the answer at 16 weeks was a 45 percent fall in the response with nothing moving underneath.

What is on the record, and what I could not find

WADA names examorelin, which is hexarelin, explicitly under section S2.2.4: prohibited at all times, in and out of competition, and non-Specified, the more serious tier. There is no FDA approval, and an openFDA query for the substance name returns no matches. I found no EMA record and no approval anywhere else, which is not the same as establishing that none exists. On compounding it is absent from everything, a gap rather than a clearance: not on the Category 2 list of substances that may present significant safety risks, whose 14 entries include GHRP-2, GHRP-6 and ipamorelin acetate, and not on the 503B Bulks List. Its two closest structural relatives, GHRP-6 and GHRP-2, were both nominated; this one most likely never was. Go and search ClinicalTrials.gov for hexarelin, then for ipamorelin. You get nothing, then three, so the registry is working. Nearly all human hexarelin work was published between 1994 and 2002, before registration was routine.

I found no dedicated toxicology programme, and no repeat-dose, genotoxicity, reproductive or carcinogenicity study surfaced in my searches; unlike ipamorelin, no FDA review document records a regulator going looking, so this absence is mine. I found no published analysis of what is in illicit hexarelin vials either, the nearest hit being a screening method covering 25 peptides rather than a survey of seized product (PMID 26003685). And the vendor side-effect lists, water retention, paraesthesia, flushing, hunger, fatigue, I could not trace to any published human trial.

My opinion

Most compounds here fail because nobody ever ran the study. Hexarelin is the opposite: somebody ran it, at the dose people inject, by the route people inject, for four months, and published the numbers.

The cycling convention is what I keep turning over. Breaks are sold as a way to manage desensitisation, which concedes the central finding rather than answering it, and the thing those breaks protect is a growth hormone spike that, in the one study measuring it at that dose and route, never produced an IGF-1 rise to begin with. The cardiac work I would rather were not attached to a sales page at all, because the growth-hormone-matched experiment is genuinely good, and what surrounds it is a rat protocol at 53 times the human dose and a receptor paper in which the compound narrowed coronary vessels.

If you run hexarelin in cycles, I want to know what you were told the break was for, and whether anyone ever put your own IGF-1 on a blood test before and after one.

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This content is for educational and informational purposes only and is not medical advice. Peptides discussed are research compounds and may not be approved for human use. Nothing here should be used to diagnose, treat, cure, or prevent any disease. Always consult a qualified healthcare professional before starting any peptide, supplement, or protocol. Individual responses vary. Do not self-administer compounds without proper medical supervision.