Ipamorelin vs GHRP-6: Head-to-Head Comparison

Both ipamorelin and GHRP-6 stimulate GH release through the ghrelin receptor, but their secondary hormonal effects differ dramatically.

Ipamorelin: The Selective Secretagogue

Ipamorelin (Aib-His-D-2-Nal-D-Phe-Lys-NH2) is a synthetic pentapeptide that was specifically designed for maximal GH selectivity. Landmark research by Raun et al. (1998) established ipamorelin as the first GH secretagogue with selectivity comparable to GHRH itself.^[1]

• GH-specific release: Ipamorelin stimulates GH release from pituitary somatotroph cells in a dose-dependent manner without significantly affecting other pituitary hormones.
• No cortisol elevation: Even at doses more than 200-fold higher than the ED50 for GH release, ipamorelin did not produce cortisol or ACTH levels significantly different from GHRH stimulation alone. This is a critical distinction from GHRP-6 and GHRP-2.^[1]
• No prolactin effect: Ipamorelin does not significantly alter prolactin, FSH, LH, or TSH levels at GH-stimulating doses.
• Minimal appetite stimulation: Unlike GHRP-6, ipamorelin produces little to no hunger response, making it more practical for researchers studying GH effects independent of appetite changes.

GHRP-6: The Potent but Non-Selective Secretagogue

GHRP-6 (His-D-Trp-Ala-Trp-D-Phe-Lys-NH2) is one of the original synthetic GH-releasing peptides, developed in the 1980s. It produces robust GH release but activates multiple hormonal pathways:^[2]

• Potent GH release: GHRP-6 is among the more potent GH secretagogues, producing substantial acute GH elevation from pituitary somatotrophs.
• Cortisol and ACTH elevation: GHRP-6 significantly increases ACTH and cortisol levels. In clinical studies, cortisol elevation was observed alongside GH release, complicating research where cortisol changes could confound results.^[3]
• Prolactin release: GHRP-6 produces moderate prolactin elevation, an effect not shared by ipamorelin.
• Strong appetite stimulation: GHRP-6 acts as a potent ghrelin mimetic, triggering substantial hunger within 20 minutes of administration. This effect is mediated through hypothalamic appetite centers.

Both peptides have been studied in human subjects, though neither is currently FDA-approved for therapeutic use.

Ipamorelin Research

• Selectivity studies: The foundational Raun et al. (1998) study in swine demonstrated that ipamorelin released GH with a potency and efficacy comparable to GHRP-6 but without affecting ACTH, cortisol, prolactin, or other pituitary hormones even at supraphysiological doses.^[1]
• Pharmacokinetic studies: Human PK/PD modeling showed ipamorelin induces GH release at all dose levels, with a half-maximal stimulation concentration (SC50) of 214 nmol/L.^[4]
• Post-surgical recovery: Ipamorelin was evaluated in clinical trials for post-operative ileus (delayed bowel recovery after surgery), showing potential to accelerate GI recovery through GH-mediated pathways.
• Body composition: Preclinical studies suggest ipamorelin can increase lean body mass and reduce adiposity through sustained GH elevation without the confounding effects of cortisol elevation.

GHRP-6 Research

• GH release characterization: Multiple studies have confirmed GHRP-6’s potent GH-releasing activity and characterized its dose-response relationship for GH, ACTH, cortisol, and prolactin.^[2]
• Appetite research: GHRP-6’s ghrelin-mimetic appetite stimulation has been studied as a model for understanding hunger signaling, with food intake increasing by 35.9% compared to placebo in controlled settings.^[3]
• Cardioprotective effects: Research suggests GHRP-6 may have direct cardioprotective effects independent of GH release, mediated through CD36 receptors in cardiac tissue.
• Cytoprotection: Cuban research groups have extensively studied GHRP-6’s protective effects against ischemia-reperfusion injury in multiple organ systems.

Ipamorelin and GHRP-6 share similar dosing ranges but differ in practical considerations related to their side effect profiles.

Ipamorelin Dosing

• Standard dose: 100–300 mcg subcutaneous injection, 1–3 times daily.
• Timing: Typically administered before bed (to augment nocturnal GH release), upon waking, and/or before workouts. Best on an empty stomach.
• Combination use: Frequently combined with CJC-1295 (without DAC) for synergistic GH release through complementary GHRH + GHS pathways.
• Cycle length: Research protocols commonly run 8–12 weeks.

GHRP-6 Dosing

• Standard dose: 100–300 mcg subcutaneous injection, 1–3 times daily.
• Timing: Similar timing principles to ipamorelin, though the strong hunger response should be anticipated 15–20 minutes post-injection.
• Saturation dose: Research indicates diminishing GH returns above approximately 100 mcg per injection (1 mcg/kg body weight), though higher doses can still be used.
• Appetite consideration: The pronounced hunger effect makes GHRP-6 impractical for researchers trying to maintain caloric restriction protocols.

The primary practical difference is that ipamorelin can be used flexibly without managing hunger spikes or cortisol elevation, while GHRP-6 requires planning around its appetite and hormonal effects.

Ipamorelin’s selectivity translates directly into a cleaner side effect profile compared to GHRP-6.

Ipamorelin Side Effects

• Generally well-tolerated: The most commonly reported effects are transient headache, mild nausea (usually at higher doses), and injection site irritation.
• No cortisol elevation: The absence of ACTH/cortisol stimulation eliminates concerns about cortisol-related side effects such as anxiety, blood sugar disruption, and immune suppression.
• No appetite disruption: The minimal hunger effect makes ipamorelin suitable for use in fasted states without discomfort.
• Water retention: Mild water retention has been reported, consistent with GH-mediated effects on sodium and fluid balance.

GHRP-6 Side Effects

• Intense hunger: The most prominent side effect. GHRP-6 triggers pronounced appetite within 15–20 minutes of injection, which can be difficult to manage and may confound body composition research.
• Cortisol elevation: GHRP-6’s stimulation of ACTH and cortisol can produce anxiety, elevated blood sugar, and potentially counteract some of GH’s beneficial effects on body composition.^[2]
• Prolactin increase: Moderate prolactin elevation may cause issues with repeated use, including potential effects on reproductive hormone balance.
• Water retention and tingling: Numbness or tingling in extremities and water retention are commonly reported.

Ipamorelin’s selectivity makes it the clearly better-tolerated option, with fewer hormonal side effects and no significant appetite disruption.

The selectivity difference between ipamorelin and GHRP-6 creates distinct ideal use cases for each peptide.

Ipamorelin Is Preferred For:

• Clean GH elevation: When the research goal is isolated GH stimulation without cortisol, prolactin, or appetite confounders.
• Fat loss protocols: The absence of appetite stimulation makes ipamorelin compatible with caloric restriction, unlike GHRP-6.
• Combination protocols: Ipamorelin + CJC-1295 (no DAC) has become the most popular research combination for synergistic GH release with minimal side effects.
• Long-term research: Better suited for extended protocols where chronic cortisol elevation from GHRP-6 could become problematic.
• Anti-aging and recovery research: The clean hormonal profile makes ipamorelin ideal for studying GH’s effects on aging, sleep, and tissue repair without confounding variables.

GHRP-6 May Be Preferred For:

• Appetite stimulation research: GHRP-6’s hunger effect can be therapeutically useful for individuals with low appetite, muscle wasting, or recovery from illness where increased caloric intake is beneficial.
• Maximum GH pulse research: Some researchers prefer GHRP-6 for its potent acute GH release, though ipamorelin’s selectivity typically outweighs this marginal potency advantage.
• Cardioprotection research: GHRP-6’s unique CD36-mediated cardioprotective effects may be relevant for cardiac research independent of GH release.
• Budget considerations: GHRP-6 is often available at a lower cost per dose than ipamorelin.