What is Hexarelin?

Compound Spotlight

Hexarelin is a six-amino-acid peptide built to release growth hormone, and in early human studies it did that more strongly than GHRH itself. The more unusual part of its story came later, when researchers looking for its binding site in the heart found it attached to a receptor that has nothing to do with growth hormone.

Where it comes from

Hexarelin belongs to the GHRPs, small synthetic peptides designed to stimulate growth hormone release. Its sequence is histidine, a D-tryptophan carrying a methyl group at the 2-position of its indole ring, alanine, tryptophan, D-phenylalanine and lysine amide.

Turin researchers described it in 1994 as a new synthetic hexapeptide. In 12 healthy young volunteers, an intravenous injection of hexarelin produced about twice the growth hormone response of the same weight-based amount of GHRH, and the response was highly reproducible on repeat testing.

Like other GHRPs, hexarelin acts on the growth hormone secretagogue receptor (GHS-R1a), the receptor for ghrelin. A 2014 review described it as chemically more stable and functionally more potent than ghrelin. Our secretagogues overview covers how this family differs from GHRH analogs.

The second receptor: CD36

By the late 1990s hexarelin was known to have cardiovascular effects, and the question was which receptor was responsible. In 2002 a Montreal group labeled rat cardiac membranes with a light-activated radioactive hexarelin derivative and purified the protein it bound. The N-terminal sequence matched rat CD36, a multifunctional glycoprotein expressed on cardiomyocytes and microvascular endothelial cells.

In perfused hearts, hexarelin raised coronary perfusion pressure in a dose-dependent manner, which indicates coronary vasoconstriction. The effect was absent in hearts from CD36-null mice and from a hypertensive rat strain genetically deficient in CD36. The authors suggested CD36 might be involved in coronary vasospasm. In that model, CD36 activation was not a simple protective signal.

Work from the same research community extended the CD36 story to lipid handling. In macrophages, hexarelin binding to CD36 and GHS-R1a activated PPAR-gamma, increased the cholesterol transporters ABCA1 and ABCG1, and enhanced cholesterol efflux; apolipoprotein E-null mice on a lipid-rich diet developed smaller atherosclerotic lesions with hexarelin. In cultured adipocytes, hexarelin reduced lipid content and increased markers of mitochondrial activity, and the corresponding changes in mouse white fat were lost in CD36-null mice.

Cardiac effects in animal models

The key experiment for separating hexarelin’s cardiac action from growth hormone used hypophysectomized rats, which have no pituitary and therefore cannot release growth hormone. After a week of hexarelin, their isolated hearts were protected against ischemia-reperfusion damage: lower left ventricular end-diastolic pressure, lower coronary perfusion pressure, less creatine kinase release and better recovery of contractility. Growth hormone produced similar results.

The control made the study informative. EP 51389, another GHRP that does not bind cardiac tissue, had no protective effect. The authors concluded that hexarelin’s effect was not mediated by growth hormone and likely involved specific cardiac receptors, a conclusion that CD36 later appeared to explain. A 2014 review summarizes later rodent work, including myocardial infarction models, though all of it remains preclinical.

Desensitization with repeated exposure

A practical question for any GHRP is whether the response holds up over time. Rahim, O’Neill and Shalet studied this in healthy adult volunteers given hexarelin repeatedly for 16 weeks. The growth hormone response to a test injection fell from an area under the curve of 19.1 at baseline to 13.1 at week 1, 12.3 at week 4 and 10.5 at week 16. Four weeks after stopping, it returned to 19.4, no different from baseline. IGF-1, body fat, lean mass and bone density did not change significantly.

The authors described the attenuation as partial and reversible. A companion analysis looked at the hormones that GHRPs also tend to release. Acute increases in ACTH, cortisol and prolactin had been reported after single GHRP injections. Over 16 weeks, the cortisol response to hexarelin decreased and then returned to baseline after the break, while the prolactin response did not change.

What the evidence supports

That hexarelin releases growth hormone in humans is established by small physiological studies from the 1990s, such as the 12-volunteer study from Turin. The desensitization data come from one 16-week study in a small group of adult volunteers. Neither line of work led to an approved product.

The CD36, cardiac and lipid findings are preclinical: isolated perfused hearts, rodent models, knockout mice and cultured cells. They are mechanistically coherent, and the CD36-null controls are a real strength. They also include a vasoconstrictive effect that sits uneasily with a purely cardioprotective reading. Whether any of it applies to people has not been tested in controlled trials.

Frequently asked questions

Is hexarelin a fragment of ghrelin?

No. It is a fully synthetic hexapeptide containing D-amino acids and a methylated tryptophan. It activates the ghrelin receptor but shares no sequence with ghrelin.

Why is CD36 binding significant?

Because it gives hexarelin a second target unrelated to growth hormone. Effects that persist in animals without a pituitary, and disappear in CD36-null animals, point to CD36 rather than the GH axis.

Does the growth hormone response fade over time?

In the one long-term human study, it fell partially over 16 weeks of repeated exposure and returned to baseline four weeks after stopping.

How do I know what is actually in the vial?

Every lot we sell has a published Certificate of Analysis from an independent, third-party lab confirming identity and purity. Lot numbers on the vial should match the COA you are referencing.

References

• Ghigo E, et al. Growth hormone-releasing activity of hexarelin, a new synthetic hexapeptide, after intravenous, subcutaneous, intranasal, and oral administration in man. J Clin Endocrinol Metab. 1994;78(3):693–698.
• Locatelli V, et al. Growth hormone-independent cardioprotective effects of hexarelin in the rat. Endocrinology. 1999;140(9):4024–4031.
• Bodart V, et al. CD36 mediates the cardiovascular action of growth hormone-releasing peptides in the heart. Circ Res. 2002;90(8):844–849.
• Avallone R, et al. A growth hormone-releasing peptide that binds scavenger receptor CD36 and ghrelin receptor up-regulates sterol transporters and cholesterol efflux in macrophages through a peroxisome proliferator-activated receptor gamma-dependent pathway. Mol Endocrinol. 2006;20(12):3165–3178.
• Rodrigue-Way A, et al. A growth hormone-releasing peptide promotes mitochondrial biogenesis and a fat burning-like phenotype through scavenger receptor CD36 in white adipocytes. Endocrinology. 2007;148(3):1009–1018.
• Rahim A, et al. Growth hormone status during long-term hexarelin therapy. J Clin Endocrinol Metab. 1998;83(5):1644–1649.
• Rahim A, et al. The effect of chronic hexarelin administration on the pituitary-adrenal axis and prolactin. Clin Endocrinol (Oxf). 1999;50(1):77–84.
• Mao Y, et al. The cardiovascular action of hexarelin. J Geriatr Cardiol. 2014;11(3):253–258.

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For laboratory and research use only. Not for human consumption. Hexarelin is not approved by the FDA for any use, and its cardiac and metabolic research is limited to animal and cell studies. This article summarizes published research for informational purposes and is not medical advice, nor a recommendation or protocol for use.

Related research compounds

Arc Peptides supplies these compounds, each third-party tested for purity and identity with a lot-specific Certificate of Analysis:

• Hexarelin

For laboratory research use only. Not for human consumption.