GHRP-1

GHRP-1 (Growth Hormone Releasing Peptide-1), also known as KP-101, is a synthetic heptapeptide designed to stimulate growth hormone (GH) release through the ghrelin receptor (GHS-R1a), a pathway distinct from endogenous GH-releasing hormone (GHRH). First synthesized in the early 1990s as part of the GHRP family, GHRP-1 stimulates pulsatile GH secretion in a dose-dependent manner through calcium-mediated mechanisms, with synergistic effects when combined with GHRH. Beyond its primary function as a growth hormone secretagogue, research has identified unexpected cytoprotective properties, including cardioprotective effects during ischemia/reperfusion and potential neuroprotective benefits. GHRP-1 was investigated in a Phase II clinical trial (NCT00381602) for end-stage renal disease patients on hemodialysis, though results remain unpublished. Currently, GHRP-1 is banned by the World Anti-Doping Agency (WADA) and has not received FDA approval for therapeutic use. It remains available exclusively as a research peptide from specialized vendors for laboratory investigations.

Growth Hormone Stimulation

• Potent GH Release: GHRP-1 increases GH secretion in a dose-dependent manner up to 3-fold in pituitary cell cultures, with a half-maximal effective dose of 10⁻⁷ M ^[1][4]
• Synergistic Effects with GHRH: When combined with GH-releasing hormone, GHRP-1 produces synergistic GH release significantly greater than either compound alone, suggesting complementary mechanisms of action ^[5][6]
• Pulsatile GH Pattern: GHRP-1 promotes physiological, pulsatile GH release subject to negative feedback, potentially avoiding supra-therapeutic hormone levels and their complications ^[7]
• Distinct Receptor Mechanism: Acts through the ghrelin receptor (GHS-R1a) via calcium-dependent, cAMP-independent pathways, providing an alternative approach to GH axis modulation ^[1][8]

Cardioprotective Properties

• Ischemia/Reperfusion Protection: GHRP family members prevent cardiac cell death and restore critical cardiac functions during ischemia/reperfusion episodes through CD36 receptor activation and prosurvival pathways ^[2][9]
• Antioxidant Defense: GHRPs reduce reactive oxygen species spillover, enhance antioxidant defenses, and decrease inflammation in cardiac tissue ^[2][10]
• Positive Inotropic Effects: GHRP-1 produces positive inotropic responses in cardiomyocytes through calcium mobilization mechanisms without chronotropic effects ^[2]

Body Composition and Metabolic Effects

• IGF-1 Stimulation: GHRP-1 increases insulin-like growth factor-1 (IGF-1) levels, which mediates muscle protein synthesis, satellite cell activation, and tissue repair ^[11][12]
• Potential Lean Mass Benefits: As a potent GH and IGF-1 stimulator, GHRP-1 theoretically supports lean body mass preservation, though well-controlled clinical studies in healthy individuals are limited ^[7][11]
• Malnutrition Applications: Investigated for improving nutritional status in end-stage renal disease patients on hemodialysis, with potential benefits for appetite and body composition ^[3]

Research Applications

• Pharmacological Tool: GHRP-1 serves as a valuable research compound for understanding GH secretion pathways, receptor mechanisms, and cytoprotective signaling cascades ^[4][6][8]

Clinical Safety Profile

• Limited Long-Term Data: GHRP-1 has been studied primarily in short-term in vitro and animal models, with limited published human clinical trial data beyond the Phase II study in ESRD patients ^[3][7]
• General GHRP Class Safety: Within the broader GHRP family, growth hormone secretagogues appear relatively safe in short-term studies, with few serious adverse events reported, though safety data are constrained by small sample sizes and brief durations ^[7][12]
• Cardiovascular Considerations: While GHRPs demonstrate cardioprotective properties in preclinical models, one clinical trial with the GH secretagogue ibutamoren was stopped early due to increased congestive heart failure rates (6.5% vs 1.7% placebo) in elderly patients recovering from hip fracture ^[12]
• Metabolic Effects: Some concern exists for increases in blood glucose due to decreases in insulin sensitivity with GH secretagogue use, requiring monitoring in susceptible individuals ^[7][12]

Regulatory Status

• Not FDA Approved: GHRP-1 has not received FDA approval for any therapeutic indication and remains an investigational compound ^[3][7]
• WADA Prohibited: Explicitly banned by the World Anti-Doping Agency under S2 (peptide hormones, growth factors, related substances, and mimetics) as a performance-enhancing substance ^[13]
• Research Use Only: Available exclusively from specialized peptide vendors for laboratory research purposes, not for human consumption or therapeutic use ^[14][15]
• Compounding Restrictions: Following FDA actions in 2023-2024, many GHRP compounds face restrictions on compounding pharmacy use, though GHRP-1 was not specifically addressed in recent regulatory updates

Side Effects and Contraindications

• Mild Adverse Effects: In studies of related GHRPs, mild facial flushing (1-3 minutes duration), soft stools, and upset stomach have been reported ^[5][12]
• Contraindications: Due to effects on GH/IGF-1 axis, caution is warranted in individuals with active malignancies, uncontrolled diabetes, or history of heart failure ^[7][12]
• Drug Interactions: Potential interactions with somatostatin, which inhibits GHRP-1-induced calcium influx and GH release ^[1][4]

Research Gaps

• Long-Term Safety Unknown: Comprehensive long-term safety data, particularly regarding cancer risk and mortality with extended use, remains lacking for GHRP-1 specifically ^[7][12]
• Human Clinical Evidence: The Phase II trial results (NCT00381602) in ESRD patients have not been published, limiting understanding of GHRP-1's safety and efficacy profile in humans ^[3]
• Optimal Dosing: Dose-response relationships, therapeutic windows, and optimal administration protocols in humans require further investigation ^[4][6]
• Population-Specific Risks: Safety profiles in special populations (elderly, pediatric, those with comorbidities) need more rigorous evaluation ^[7][12]