Hexarelin

In simple words

Hexarelin is one of the most potent man-made peptides that boost growth hormone release. Its ability to protect heart muscle is of special interest, but so far this has only been shown in mice.

What this molecule is

6 aa: His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH₂. Synthetic GHRP with methylated Trp for ↑stability. ~887 Da.

Why it is studied

One of the most potent GHRPs for GH stimulation. Unique property: cardioprotection via the CD36 receptor (independent of GHS-R1a). ↓myocardial fibrosis, ↓infarct size in mice. The only GHRP with cardioprotective activity in ischemia/reperfusion models.

How it works

Dual: GHS-R1a (↑GH) + CD36 scavenger receptor on cardiomyocytes (↑autophagy, ↓mTOR, ↓MDM2/p53, ↓caspase-3). Cardioprotection via MAPK/PI3K/Akt, independent of the GH effect. Neuroprotection: Neuro-2A, MAPK/PI3K/Akt.

Doses used in studies

Studies used 100-200 mcg SC 2-3 times/day in cycles of 4 weeks on / 2 weeks off (GHS-R1a desensitization sets in quickly), for a course of 2-3 months.

Combined with in studies

• Sermorelin / Mod-GRF — GHRH + GHRP for GH
• GHRP-6 — DO NOT combine: competition for GHS-R1a and ↑side effects

Level of evidence

Level B-C Human observational data. There are studies in humans, but they are small, uncontrolled, or cohort studies. The data are encouraging but need confirmation. Phase I/II in humans (GH). Cardioprotection: animals only.

Important to know

⚠️ Cardioprotection: mouse models only! No clinical data. ↑cortisol/prolactin (unlike ipamorelin). GHS-R1a desensitization: cycling is mandatory. Not approved.

Studies in PubMed

1. Hexarelin treatment preserves myocardial function and reduces cardiac fibrosis in a mouse model of acute myocardial infarction. (Physiol Rep, 2018)
2. Hexarelin targets neuroinflammatory pathways to preserve cardiac morphology and function in a mouse model of myocardial ischemia-reperfusion. (Biomed Pharmacother, 2020)
3. Hexarelin protects cardiac H9C2 cells from angiotensin II-induced hypertrophy via the regulation of autophagy. (Pharmazie, 2019)
4. Hexarelin Modulation of MAPK and PI3K/Akt Pathways in Neuro-2A Cells Inhibits Hydrogen Peroxide-Induced Apoptotic Toxicity. (Pharmaceuticals (Basel), 2021)
5. Hexarelin alleviates apoptosis on ischemic acute kidney injury via MDM2/p53 pathway. (Eur J Med Res, 2023)