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Hex2.8

Hexarelin Research

Mostly mechanism / observationalLimited safety

9 peer-reviewed studies

What the evidence says

Mostly mechanism / observational

Most Hexarelin studies are mechanism or observational rather than RCTs that measure a clinical effect — keep findings provisional.

Most evidence is from mixed-quality studies published 1996–2003 with a typical study size of 12 participants.

Based on 9 studies · 100 total participants

Confidence

Low

By outcome

GH / IGF-1 secretion (biomarker, desensitizes)
Mostly mechanism / observational5 studies
Cardiovascular pharmacology (preclinical)
Mostly mechanism / observational4 studies
Off-target endocrine & safety
Too few graded studies2 studies

Older research base

Newest study from 2003

19962003

1Open-Labeln=12 · very small study1998

These results show that attenuation of the GH response after long-term hexarelin therapy is partial and reversible.

Rahim A, Shalet SM · Growth Horm IGF Res (1998)

Twice-daily subcutaneous hexarelin over 16 weeks in 12 healthy elderly individuals
Mean GH area-under-curve fell from 19.1 to 10.5 µg/l/hour over the study period (significant decline by weeks 4 and 16)
After a 4-week washout the GH response recovered to near-baseline (19.4 µg/l/hour)

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2Review1998

The effect of GHS is partially desensitized but prolonged, intermittent oral administration increases insulin-like growth factor I (IGF-I) levels.

Ghigo E, Arvat E, Camanni F · Ann Med (1998)

Review of GH secretagogues including hexarelin and the GHS-R receptor pharmacology
Documents marked, dose-related, reproducible GH release across IV, SC, intranasal and oral routes
Explicitly notes the GHS effect is partially desensitized with continued use

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3Open-Labeln=7 · very small study1996

The partial suppression of pituitary hGH responsiveness to long-term intranasal hexarelin treatment, probably due to desensitization, does not affect the observed increase in growth velocity.

Klinger B, Silbergeld A, Deghenghi R, Frenkel J, Laron Z · Eur J Endocrinol (1996)

Prospective study of intranasal hexarelin (60 µg/kg t.i.d.) in 7 prepubertal short children over 6-10 months
Peak GH response to a hexarelin bolus dropped after just 7 days of treatment and remained suppressed during dosing
GH responsiveness partially recovered 3 months after stopping treatment

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4Open-Labeln=26 · very small study2001

In humans, the acute administration of hexarelin exerts a GH-independent positive inotropic effect likely mediated by specific GHRPs myocardial receptors.

Broglio F, Benso A, Valetto MR, Gottero C, Quaranta L, Podio V, et al. · Endocrine (2001)

Acute IV hexarelin (2 µg/kg) in 7 normal adults, 7 GH-deficient patients, and 12 dilated-cardiomyopathy patients
Significantly increased left-ventricular ejection fraction in normal and GH-deficient subjects — including GH-deficient patients in whom hexarelin did NOT raise GH
No significant change in mean blood pressure or heart rate

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5Open-Labeln=36 · small study1998

Hexarelin is a powerful stimulus of GH secretion in pubertal children and in adults but not in prepubertal children and in elderly subjects.

Bellone J, Bartolotta E, Sgattoni C, Aimaretti G, Arvat E, Bellone S, et al. · J Endocrinol Invest (1998)

Compared GH responses to hexarelin (2 µg/kg IV) vs GHRH ± arginine across prepubertal/pubertal children, young adults and elderly
Hexarelin produced a marked GH rise in pubertal children and young adults
The GH response was notably weaker in prepubertal children and in the elderly

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6Open-Labeln=7 · very small study1999

HEX increased LVEF (70.7+/-3.0 vs 64.0+/-1.5%, p<0.03) without significant changes in MBP and HR... This effect seems GH-independent and might be mediated by specific GHS myocardial receptors.

Bisi G, Podio V, Valetto MR, Broglio F, Bertuccio G, Del Rio G, et al. · J Endocrinol Invest (1999)

Acute IV hexarelin (or recombinant human GH) in 7 male volunteers, cardiac performance measured by radionuclide angiocardiography
Hexarelin acutely raised left-ventricular ejection fraction (64.0 → 70.7%, p<0.03); GH alone, raising circulating GH to the same extent, did not — a GH-independent inotropic effect
Hexarelin (but not GH) significantly raised cortisol; blood pressure, heart rate, aldosterone and catecholamines were unchanged

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7Open-Labeln=12 · very small study1998

Like other GHS, HEX possesses also PRL-, ACTH- and cortisol-releasing activity but the mechanisms underlying these effects are even less clear.

Arvat E, Maccagno B, Ramunni J, Broglio F, Lanfranco F, Giordano R, et al. · J Endocrinol Invest (1998)

Acute hexarelin (2 µg/kg IV) in 12 normal young women
Hexarelin produced a large GH response and also significantly raised prolactin, ACTH and cortisol
Documents the off-target HPA-axis and prolactin stimulation of the GHS class — not GH-selective

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8Animal2003

Hexarelin effects are mediated in part by the GHS-R and largely by interactions with the CD36.

Torsello A, Bresciani E, Rossoni G, Avallone R, Tulipano G, Cocchi D, et al. · Endocrinology (2003)

Isolated-heart ischemia/reperfusion model after 7-day in-vivo pretreatment in rats
Hexarelin (80 µg/kg) markedly outperformed ghrelin at preventing ischemia-reperfusion damage (≈60% vs 15% protection)
Identifies the scavenger receptor CD36 as the dominant mediator of hexarelin's cardiac effect, alongside GHS-R

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9Animal1998

In vivo administration of hexarelin for 21 days resulted in a striking heart protection against reperfusion stunning.

Rossoni G, De Gennaro Colonna V, Bernareggi M, Polvani GL, Müller EE, Berti F · J Cardiovasc Pharmacol (1998)

Isolated senescent (24-month-old) rat hearts subjected to ischemia/reperfusion
21-day subcutaneous hexarelin (80 µg/kg b.i.d.) largely preserved post-ischemic left-ventricular developed pressure and limited creatine-kinase release
Supports a cardioprotective pharmacology in aged animal hearts

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View in Research Library

Hexarelin Research

Mostly mechanism / observational

Does desensitization to hexarelin occur?

Orally active growth hormone secretagogues: state of the art and clinical perspectives.

Desensitization from long-term intranasal treatment with hexarelin does not interfere with the biological effects of this growth hormone-releasing peptide in short children.

Growth hormone-independent cardiotropic activities of growth hormone-releasing peptides in normal subjects, in patients with growth hormone deficiency, and in patients with idiopathic or ischemic dilated cardiomyopathy.

Hexarelin, a synthetic GH-releasing peptide, is a powerful stimulus of GH secretion in pubertal children and in adults but not in prepubertal children and in elderly subjects.

Acute cardiovascular and hormonal effects of GH and hexarelin, a synthetic GH-releasing peptide, in humans.

Influence of galanin and serotonin on the endocrine response to Hexarelin, a synthetic peptidyl GH-secretagogue, in normal women.

Ghrelin plays a minor role in the physiological control of cardiac function in the rat.

Protectant activity of hexarelin or growth hormone against postischemic ventricular dysfunction in hearts from aged rats.