Background
While GHRP-2’s capacity to stimulate GH release was well established, its metabolic consequences — particularly effects on substrate oxidation and energy expenditure — had not been characterized in controlled human studies. GH is a known lipolytic hormone, and defining whether acute GHRP-2 infusion could shift substrate utilization toward fat oxidation would help characterize its metabolic relevance.
Methods
Twelve healthy adult male volunteers participated in a randomized, crossover, single-dose metabolic study. Subjects received:
- GHRP-2 at 1 µg/kg/h IV infusion for 3 hours
- Saline placebo infusion for 3 hours (separate session, washout period)
Measurements collected throughout infusion:
- Serum GH at 30-minute intervals
- Indirect calorimetry (energy expenditure, respiratory quotient)
- Serum insulin, glucose, free fatty acids
- Urine nitrogen (protein oxidation estimate)
Key Findings
- GH: GHRP-2 infusion produced sustained GH elevation throughout the 3-hour window (~4–8 µg/L mean vs. <1 µg/L with placebo)
- Substrate oxidation: Respiratory quotient (RQ) fell from ~0.87 to ~0.82 during GHRP-2 infusion, indicating a significant shift toward fat oxidation
- Free fatty acids: Modest FFA elevation consistent with GH-mediated lipolysis
- Energy expenditure: Slight but non-significant increase in total EE (~3%) during GHRP-2 vs. placebo
- Glucose/insulin: No clinically significant changes in the 3-hour window; mild late-phase glucose elevation expected with prolonged GH exposure was not captured in this short protocol
- No adverse events of clinical significance reported
Clinical Significance
This study provided early evidence that GHRP-2 can shift substrate metabolism toward fat utilization via GH-mediated lipolysis in humans. The effect is consistent with GH physiology:
“GH is fundamentally a fat-mobilizing hormone, and its pulsatile secretion promotes fatty acid availability between meals.”
For practitioners using GHRP-2 in body composition protocols, these data support a mechanistic basis for increased fat oxidation with pulsatile GHRP-2 dosing — though longer-term, prospective body composition studies are needed to quantify the clinical magnitude.
Limitations
- Short duration (3-hour infusion); cannot be extrapolated to chronic SC pulsatile dosing patterns
- Small n (12 male participants only)
- IV infusion kinetics differ from SC administration used clinically
- Glucose counter-regulation and long-term IGF-1 effects were not assessed