Hexarelin strengthens the contraction of the heart regardless of how much growth hormone it releases. In a 1999 study in healthy men, the left ventricular ejection fraction rose after hexarelin from 64 to 71 percent, while growth hormone given in the same amount did not change it at all. A similar effect was measured in patients with growth hormone deficiency and during coronary bypass surgery. Below you will find which receptors hexarelin uses to act on the heart, what each study measured and what these results do not yet tell us.
Why does hexarelin act on the heart?
Hexarelin has its own receptors in the heart, so it acts on it directly and not through growth hormone. It belongs to the GHRP family, the growth hormone releasing peptides. In the pituitary it works through the ghrelin receptor GHS-R1a, just like GHRP-2, GHRP-6 and ipamorelin. Receptors for this group of peptides have, however, also been found in the heart muscle.
The second target of hexarelin in the heart is the protein CD36. It was described by researchers from the University of Montreal in 2002, in Circulation Research. Hexarelin binds to it independently of the ghrelin receptor, so it has two separate routes to the heart. The general profile of hexarelin, including its effect on hormones and sleep, is covered in the guide hexarelin: what human research shows.
What did the study in healthy men show?
In seven healthy men, hexarelin given intravenously increased the left ventricular ejection fraction from 64.0 to 70.7 percent. The study was carried out at the University of Turin and published in the Journal of Endocrinological Investigation in 1999. Ejection fraction is the share of blood that the left ventricle pushes out with each beat. It was measured with an isotope method, radionuclide angiocardiography.
In a separate trial, the same men received recombinant growth hormone. Both substances raised the blood level of growth hormone to the same degree. Even so, the ejection fraction rose only after hexarelin. Blood pressure and heart rate did not change significantly in either trial.
The effect appeared quickly and was short-lived. The ejection fraction rose significantly after 15 minutes, peaked after 30 minutes and held for up to 60 minutes. The authors concluded that hexarelin has a short-acting effect that strengthens the contraction of the heart. In their view, this effect does not depend on growth hormone but on receptors in the heart muscle.
Does hexarelin act on the heart in growth hormone deficiency?
Yes, in men with severe growth hormone deficiency hexarelin also increased the ejection fraction. The second study from Turin appeared in 1999 in the European Journal of Pharmacology. It included seven patients with growth hormone deficiency, with a mean age of 42, and nine healthy men.
In the patients, hexarelin released almost no growth hormone, because their pituitary was not capable of it. The peak was 1.9 micrograms per litre against 45.7 in the healthy men. The ejection fraction in the patients nevertheless rose from 50 to 57 percent. In the healthy men it rose from 63 to 70 percent. This is the strongest argument that the effect on the heart does not go through growth hormone.
| Group | Ejection fraction before | Peak after hexarelin |
|---|---|---|
| Healthy men (1999, J Endocrinol Invest) | 64.0 percent | 70.7 percent |
| Healthy men (1999, Eur J Pharmacol) | 63 percent | 70 percent |
| Growth hormone deficiency | 50 percent | 57 percent |
| Ischaemic cardiomyopathy | 22.6 percent | 26.2 percent |
| Dilated cardiomyopathy | 16.7 percent | 17.7 percent (no significant change) |
What was measured in patients with heart disease?
In patients with ischaemic cardiomyopathy hexarelin increased the ejection fraction, while in patients with dilated cardiomyopathy it did not. The results were published in the European Journal of Heart Failure in 2002. The study included five patients with the ischaemic form and eight with the dilated form. All had very weak left ventricular function, with an ejection fraction between the mid teens and the mid twenties.
In both groups hexarelin raised growth hormone to a similar degree. In the ischaemic form the ejection fraction rose from 22.6 to 26.2 percent. In the dilated form it stayed practically unchanged. The authors explain the difference by the fact that more living muscle remains in ischaemic disease, which can respond to the stimulus.
What did the study during heart surgery show?
In 24 men with coronary artery disease, hexarelin given during bypass surgery improved heart function within 10 minutes. The study was published in the European Journal of Pharmacology in 2002. The patients were under general anaesthesia, and heart function was measured with transoesophageal echocardiography and a pulmonary artery catheter. Four groups were compared: hexarelin at a dose of 2 micrograms per kilogram, GHRH, growth hormone and placebo.
Only hexarelin increased the ejection fraction, the cardiac index and the cardiac output. The effect lasted up to 90 minutes. Pulmonary capillary wedge pressure fell, which means a lower load on the left ventricle. Peripheral vascular resistance did not change, and heart rate was the same as after placebo. GHRH and growth hormone had no effect on heart function, even though GHRH raised growth hormone about as much as hexarelin did.
What role does the CD36 receptor play?
CD36 is a protein on the surface of heart muscle cells and small blood vessels, to which hexarelin binds independently of the ghrelin receptor. The Montreal team found it in 2002 by labelling cell membranes from rat hearts with a radioactive derivative of hexarelin. The bound protein had a mass of 84 kDa and turned out to be identical to CD36.
In isolated hearts, hexarelin increased coronary perfusion pressure in proportion to the dose. There was no effect in the hearts of mice lacking CD36 or in rats with an inborn absence of this protein. This means that hexarelin constricted the coronary vessels precisely through CD36. The authors suggested that this mechanism may matter in coronary vasospasm in atherosclerosis. This is a result from animal models and does not transfer directly to humans.
What did newer animal studies show?
Newer work in rats points to a protective effect of hexarelin after cardiac ischaemia. In a 2017 study in the International Heart Journal, a coronary artery in rats was closed for 30 minutes and then blood flow was restored. For 7 days the animals received hexarelin, ghrelin or saline. Hexarelin improved the contractile function of the heart and increased the number of surviving heart muscle cells.
The effect of hexarelin was slightly stronger than that of ghrelin at an equivalent dose. Hexarelin also lowered the level of malondialdehyde, a marker of oxidative damage. The effect disappeared after the GHS-R1a receptor was blocked, so in this model it went through the ghrelin receptor in the heart.
What is not known about hexarelin and the heart?
All the human studies concerned a single intravenous dose and measured the effect for at most an hour and a half. There are no studies in which hexarelin was given for months and heart function was assessed. The groups were small, from 5 to 24 people. Hexarelin is not an approved drug for any heart condition. Most of the studies described here come from two teams, in Turin and in Montreal.
Where to buy hexarelin and how much does it cost?
In the shop, hexarelin comes in 10 mg vials from three brands, all in stock. Hexarelin 10 mg Genheal costs 45 EUR. Hexarelin 10 mg Bio-Peptide costs 50 EUR, and Hexarelin 10 mg Nouveaux Ltd. 55 EUR. All versions are listed on the hexarelin page. A comparison with related peptides is in the guide on GHRP-2, GHRP-6, ipamorelin and hexarelin.
Frequently asked questions
Does hexarelin act on the heart?
Yes. In human studies a single intravenous dose increased the left ventricular ejection fraction, in healthy men from 64 to 71 percent, with an effect lasting up to an hour.
Does the effect of hexarelin on the heart depend on growth hormone?
No. Growth hormone in the same amount did not change heart function, and in patients with growth hormone deficiency hexarelin still increased the ejection fraction.
What is the CD36 receptor?
It is a protein on heart cells and small blood vessels, to which hexarelin binds independently of the ghrelin receptor. It was described in 2002 in studies on rat and mouse hearts.
Does hexarelin help in heart failure?
In a 2002 study it improved the ejection fraction in ischaemic cardiomyopathy, but not in dilated cardiomyopathy. It is not approved as a drug for heart disease.
How quickly does hexarelin act on the heart?
In healthy men the effect was significant after 15 minutes and greatest after 30 minutes. During heart surgery the improvement appeared after 10 minutes and lasted up to 90 minutes.
Sources
- Bisi G, Podio V, Valetto MR et al. Acute cardiovascular and hormonal effects of GH and hexarelin, a synthetic GH-releasing peptide, in humans. Journal of Endocrinological Investigation, 1999, 22(4): 266-272. https://doi.org/10.1007/BF03343555
- Bisi G, Podio V, Valetto MR et al. Cardiac effects of hexarelin in hypopituitary adults. European Journal of Pharmacology, 1999, 381(1): 31-38. https://doi.org/10.1016/s0014-2999(99)00537-3
- Imazio M, Bobbio M, Broglio F et al. GH-independent cardiotropic activities of hexarelin in patients with severe left ventricular dysfunction due to dilated and ischemic cardiomyopathy. European Journal of Heart Failure, 2002, 4(2): 185-191. https://doi.org/10.1016/s1388-9842(01)00223-9
- Broglio F, Guarracino F, Benso A et al. Effects of acute hexarelin administration on cardiac performance in patients with coronary artery disease during by-pass surgery. European Journal of Pharmacology, 2002, 448(2-3): 193-200. https://doi.org/10.1016/s0014-2999(02)01934-9
- Bodart V, Febbraio M, Demers A et al. CD36 mediates the cardiovascular action of growth hormone-releasing peptides in the heart. Circulation Research, 2002, 90(8): 844-849. https://doi.org/10.1161/01.res.0000016164.02525.b4
- Huang J, Li Y, Zhang J et al. The Growth Hormone Secretagogue Hexarelin Protects Rat Cardiomyocytes From in vivo Ischemia/Reperfusion Injury Through Interleukin-1 Signaling Pathway. International Heart Journal, 2017, 58(2): 257-263. https://doi.org/10.1536/ihj.16-241