Side-by-side · Research reference
HexarelinvsHumanin
Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.
APhase 1HUMAN-REVIEWED19/45 cited
BAnimal-StrongHUMAN-REVIEWED14/52 cited
Hexarelin
Hexapeptide GHRP · Cardio-tropic
SQ · Multiple sites · 1–3×/day
Humanin
Mitochondrial-Derived Peptide · Cytoprotective
SQ · Experimental
01Mechanism of Action
Parameter
Hexarelin
Humanin
Primary target
Ghrelin receptor (GHS-R1a) + cardiac CD36Smith 1996Ghigo 1997
Pathway
GHS-R1a → Gαq → Ca²⁺ → GH release. CD36 engagement → direct cardio-tropic actionGhigo 1997
Humanin binds Bax/Bim → inhibits mitochondrial outer membrane permeabilization (MOMP) → blocks cytochrome c release → prevents caspase activation → cell survival
Downstream effect
Strong GH pulse + IGF-1 elevation; cardio-protective effects in animal MI modelsGhigo 1997
Suppression of apoptosis, mitochondrial stabilization, reduced oxidative stress, preservation of germ cells and neurons under stressZhu 2022Lue 2021Velentza 2024
Feedback intact?
Yes initially; tachyphylaxis with chronic useGhigo 1997
Not applicable — peptide acts as anti-apoptotic signal, not hormonal axis
Origin
Synthetic hexapeptide His-D-2-Methyl-Trp-Ala-Trp-D-Phe-Lys-NH₂Smith 1996
Encoded by short open reading frame in mitochondrial 16S rRNA gene (MTRNR2). 24-28 amino acids. 13 homologous variants (MTRNR2L1-L13) identified.Zhu 2022Shahzaib 2026
Antibody development
—
Not reported in animal models
02Dosage Protocols
Parameter
Hexarelin
Humanin
Frequency
1–2× per day max (tachyphylaxis with chronic 3× daily)
Daily (IP)
Lower / starter dose
50 mcg per dose
—
Evidence basis
Phase 1 / Phase 2 trialsSmith 1996Ghigo 1997
Animal models (rat, mouse)Huang 2025El 2022Velentza 2024
Duration
4–8 weeks on / 4–8 weeks off (tachyphylaxis mitigation)
8–12 weeks in animal studies
Reconstitution
Bacteriostatic water
—
Timing
Pre-sleep + fasted preferred
—
Standard experimental dose (HNG)
—
4 mg/kg IP (rat)
Most common dose in rodent models.
Ex vivo bone culture
—
1 µg/mL
Protective against venetoclax-induced bone growth retardation.
Human data
—
None — no clinical trials reported
Analog (HNG)
—
Gly[14]-humanin — more potent variant
Substitution at position 14 enhances cytoprotective activity.
03Metabolic / Fat Loss Evidence
Parameter
Hexarelin
Humanin
Direct fat loss evidence
—
None
Mechanism overlap
—
Mitochondrial health may indirectly influence metabolic efficiency, but no quantified effect
04Side Effects & Safety
Parameter
Hexarelin
Humanin
Hunger
Strong appetite increase via ghrelin agonism
—
IGF-1 elevation
Strong; monitor with chronic high-dose use
—
Cancer risk
Contraindicated in active malignancy (GH/IGF-1 axis)
—
Pregnancy / OB
Avoid
—
Animal model safety
—
Well-tolerated in rat and mouse studies at 4 mg/kg for 8–12 weeks
Human safety data
—
None — no clinical trials
Theoretical fibrillation risk
—
Induces amyloid-like fibrillation of Bax/BID. Long-term sequelae unknown.
Injection site reaction
—
Not reported in animal studies (IP route)
Reproductive safety
—
Protective in POI model (cyclophosphamide-induced), no adverse effects on fertility notedHuang 2025
Absolute Contraindications
Hexarelin
- ·Active malignancy
- ·Pregnancy / breastfeeding
- ·Disrupted hypothalamic-pituitary axis
Humanin
- ·Unknown — no human data
Relative Contraindications
Hexarelin
- ·Untreated diabetes
- ·Severe hyperprolactinemia
Humanin
- ·Active malignancy (theoretical risk of anti-apoptotic effect on tumour cells)
05Administration Protocol
Parameter
Hexarelin
Humanin
1. Reconstitution
Add 2 mL bacteriostatic water to 5 mg vial → 2.5 mg/mL = 250 mcg per 0.1 mL.
Intraperitoneal (IP) in animal models. Subcutaneous route untested. No human protocols exist.
2. Injection site
SQ — abdomen or thigh. Rotate sites.
Synthetic peptide reconstituted in sterile saline or PBS. No commercial formulation available.
3. Timing
Pre-sleep + fasted preferred. Cycle on/off to avoid tachyphylaxis.
Daily administration in animal studies. Optimal timing not characterized.
4. Storage
Lyophilised: room temp, light-protected. Reconstituted: refrigerate ≤30 days.
Lyophilised powder: -20 °C. Reconstituted: 4 °C, use within 7 days. Avoid freeze-thaw cycles.
5. Needle
29–31G, 4–8 mm insulin syringe.
No FDA approval, no IND, no clinical trials. Experimental research tool only.
06Stack Synergy
Hexarelin
+ CJC-1295 (no DAC)
StrongHexarelin (GHRP) + CJC-1295-no-DAC (GHRH analogue) is the higher-amplitude variant of the standard GHRH+GHRP stack. Hexarelin produces a stronger pulse than ipamorelin but with cortisol + prolactin signal — choose this stack for maximum GH amplitude when side-effect tolerance is acceptable. Cycle aggressively.
- Hexarelin
- 100 mcg SQ · pre-sleep
- CJC-1295 (no DAC)
- 100 mcg SQ · same injection
- Primary benefit
- Maximum GH pulse amplitude (with side-effect signal)
Humanin
+ MOTS-c
Multi-pathwayBoth are mitochondrial-derived peptides. MOTS-c enhances metabolic efficiency and insulin sensitivity via AMPK activation, while humanin prevents mitochondrial apoptosis. Combined, they address mitochondrial function (MOTS-c) and survival signaling (humanin), supporting cellular resilience under metabolic and oxidative stress.
- Humanin
- 4 mg/kg IP · daily (animal model)
- MOTS-c
- 5 mg/kg IP · daily (animal model)
- Frequency
- Once daily
- Primary benefit
- Mitochondrial health, metabolic efficiency, anti-apoptotic signaling