Key papers ✓ 4~ 1? 2

• ✓ Positive human trialLancet · 2000

  GH-releasing hormone and GH-releasing peptide-6 for diagnostic testing in GH-deficient adults.

  Humanssize not reported120 min sampling after a single test

  Multicentre diagnostic-accuracy study, GHRH/GHRP-6 test vs insulin tolerance test (ROC analysis)

  In 125 adults with pituitary disease and 125 controls, a combined GHRH + GHRP-6 test separated GH-deficient from healthy adults better than the insulin tolerance test, with no side-effects reported.

  Key resultMean GH peak 59.2 microg/L (SD 2.2) in controls vs 4.1 (0.3) in cases after GHRH/GHRP-6; after ITT 14.3 (1.7) vs 0.5 (0.06); differential response greater for GHRH/GHRP-6 (p<0.001)

  Study details

  Studied

  Adults with organic pituitary disease (GH-deficient, ITT GH peak <= 3 microg/L) and healthy controls

  Compared with

  Insulin tolerance test (ITT)

  Main outcome

  Peak GH after GHRH/GHRP-6 test vs ITT

  Sample

  125 adults with organic pituitary disease plus 125 healthy controls

  Authors' conclusion

  The GHRH/GHRP-6 test is a convenient, safe and reliable test for adult GH deficiency; an evoked GH of >= 15.0 microg/L accurately distinguishes healthy from GH-deficient adults.

  Limitations

  Diagnostic test study; only 27 controls had an ITT for comparison.

  DOI 10.1016/S0140-6736(00)02755-0PubMed 11030292
• ~ Mixed human RCTNeuroendocrinology · 1995

  Growth hormone-releasing peptide-6 stimulates sleep, growth hormone, ACTH and cortisol release in normal man.

  Humanssize not reportedRandomizedPlacebo-controlledOne night (sleep EEG 23.00 to 07.00 h)

  Placebo-controlled comparison of repeated i.v. boluses (4 x 50 micrograms) on sleep EEG and hormone profiles

  In healthy men, repeated IV GHRP-6 vs placebo raised nocturnal GH (15.4 vs 5.5 ng/ml) but also ACTH and cortisol (56.0 vs 25.2 ng/ml), and increased stage 2 sleep without changing slow-wave sleep.

  Key resultGH 15.4 +/- 9.6 vs 5.5 +/- 4.0 ng/ml (p < 0.02); cortisol 56.0 +/- 31.0 vs 25.2 +/- 9.0 ng/ml (p < 0.02); stage 2 sleep 270.1 +/- 25.3 vs 245.4 +/- 25.8 min (p < 0.02)

  Study details

  Studied

  Normal male controls

  Compared with

  Placebo

  Main outcome

  Nocturnal GH, ACTH, cortisol and sleep EEG

  Sample

  Number of subjects not given in the abstract (normal male controls)

  Authors' conclusion

  GHRP stimulates not only GH release but also ACTH and cortisol secretion; it enhances stage 2 sleep and does not affect slow-wave sleep.

  Limitations

  Healthy men only; abstract truncated so design details are incomplete.

  DOI 10.1159/000126883PubMed 7617137
• ? Inconclusive human trialEur J Pharm Sci · 2013

  Pharmacokinetic study of Growth Hormone-Releasing Peptide 6 (GHRP-6) in nine male healthy volunteers.

  Humans9 peopleNo control groupPlasma sampling to 12 h post-administration

  Pharmacokinetic study, single intravenous bolus at 100, 200 and 400 ug/kg

  In 9 healthy men given single IV doses, GHRP-6 had an elimination half-life of about 2.5 h with roughly dose-proportional exposure; a pharmacokinetic study with no efficacy outcome.

  Key resultDistribution half-life 7.6 +/- 1.9 min and elimination half-life 2.5 +/- 1.1 h (bi-exponential model)

  Study details

  Studied

  Healthy male volunteers

  Main outcome

  Plasma pharmacokinetics of GHRP-6 (LC-MS)

  Sample

  Nine healthy male volunteers

  Authors' conclusion

  GHRP-6 disposition fits a bi-exponential model, with a trend for AUC to increase proportionally with dose; atypical concentration spikes occurred in four of nine subjects.

  Limitations

  Small pharmacokinetic study with no efficacy outcome.

  DOI 10.1016/j.ejps.2012.10.006PubMed 23099431
• ✓ Positive human trialEur J Endocrinol · 1995

  Growth hormone-releasing effect of oral growth hormone-releasing peptide 6 (GHRP-6) administration in children with short stature.

  Humans13 people

  Single-dose comparison of oral GHRP-6 with intravenous GHRH-29 (and arginine interaction)

  In 13 children with normal short stature, a single oral GHRP-6 dose raised GH (peak 18.8 vs baseline 1.1 µg/l) similarly to IV GHRH; growth outcomes were not studied.

  Key resultOral GHRP-6 raised GH from 1.1 +/- 0.3 to 18.8 +/- 3.0 micrograms/l (p < 0.0006), similar to GHRH (2.2 +/- 0.9 to 20.8 +/- 4.5, p < 0.007)

  Study details

  Studied

  Children aged 6.2-10.5 years, prepubertal, with normal short stature

  Compared with

  Intravenous GHRH-29 1 microgram/kg

  Main outcome

  GH response

  Sample

  13 children with normal short stature

  Authors' conclusion

  Oral GHRP-6 (300 micrograms/kg) elicited a GH response similar to intravenous GHRH in children with normal short stature.

  Limitations

  Small acute study; abstract truncated; growth outcomes not studied.

  DOI 10.1530/eje.0.1330425PubMed 7581965
• ✓ Positive animalFront Pharmacol · 2024

  Growth hormone releasing peptide-6 (GHRP-6) prevents doxorubicin-induced myocardial and extra-myocardial damages by activating prosurvival mechanisms.

  Animalssize not reported

  Animal study with echocardiography, histopathology, electron microscopy and gene expression

  In rats given doxorubicin, concurrent GHRP-6 prevented ventricular dilation, preserved heart function and reduced organ damage and mortality.

  Study details

  Studied

  Otherwise healthy rats given doxorubicin

  Compared with

  Doxorubicin without GHRP-6

  Main outcome

  Prevention of dilated cardiomyopathy and organ damage

  Authors' conclusion

  GHRP-6 given with doxorubicin prevented ventricular dilation, preserved LV systolic function, attenuated extracardiac toxicity and reduced morbidity and mortality, with antioxidant and prosurvival effects. These findings are in rats.

  Limitations

  Rat study; animal numbers not given in the abstract.

  DOI 10.3389/fphar.2024.1402138PubMed 38873418Free full text
  FIGURE 2 FIGURE 3
• ✓ Positive animalPlast Surg Int · 2016

  Growth Hormone-Releasing Peptide 6 Enhances the Healing Process and Improves the Esthetic Outcome of the Wounds.

  Animalssize not reported5 days (rats); 30 days (rabbits)

  Animal study, topical GHRP-6 jelly (400 ug/mL)

  Topical GHRP-6 reduced wound inflammation in rats and prevented hypertrophic scar formation in a rabbit ear model, but did not reverse established scars.

  Study details

  Studied

  Wistar rats with excisional wounds; rabbit ear hypertrophic scar model

  Main outcome

  Wound closure, inflammatory and fibrotic markers, scar formation

  Authors' conclusion

  GHRP-6 attenuated wound inflammation and fibrotic cytokines and dramatically reduced hypertrophic scar onset in rabbits via PPARg, but had no effect on established lesions.

  Limitations

  Animal models only; no effect on consolidated scars.

  DOI 10.1155/2016/4361702PubMed 27200188Free full text
  Figure 1
• ? Inconclusive reviewSex Med Rev · 2018

  The Safety and Efficacy of Growth Hormone Secretagogues.

  No new data

  Literature review

  Review of human GH secretagogue studies: few long-term controlled studies; generally well tolerated but with concern for raised blood glucose, and long-term safety is unknown.

  Study details

  Studied

  Humans receiving GH secretagogues (GH-releasing peptides, ibutamoren)

  Main outcome

  Safety and efficacy of GH secretagogues

  Sample

  Review of clinical studies (number not stated)

  Authors' conclusion

  Few long-term controlled studies exist; GHSs are well tolerated with some concern for raised blood glucose via reduced insulin sensitivity, and long-term safety, including cancer, needs study.

  Limitations

  Few long-term, rigorously controlled studies.

  DOI 10.1016/j.sxmr.2017.02.004PubMed 28400207Free full text

Reported side effects

• reportedIncreased ACTH and cortisol release [ref]

Human exposure in published studies is mostly single doses or 7-day courses; no long-term human safety data exist.

✓ positive · ✗ negative · ~ mixed · ? inconclusive, judged on each paper's own main outcome. Grades: A strong human evidence → D little or none. Papers and verdicts are drawn from PubMed, Europe PMC and Russian journals (CyberLeninka); not medical advice.