Side-by-side · Research reference
HumaninvsLL-37
Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.
AAnimal-StrongHUMAN-REVIEWED14/52 cited
BHuman-MechanisticHUMAN-REVIEWED15/35 cited
Humanin
Mitochondrial-Derived Peptide · Cytoprotective
SQ · Experimental
LL-37
Cathelicidin · Human AMP
Broad-spectrumAntimicrobial activity
Endogenous · Secreted at inflammation sites
01Mechanism of Action
Parameter
Humanin
LL-37
Primary target
Pathway
Humanin binds Bax/Bim → inhibits mitochondrial outer membrane permeabilization (MOMP) → blocks cytochrome c release → prevents caspase activation → cell survival
hCAP-18 precursor → Proteinase-3 cleavage → LL-37 release → Membrane insertion/disruption
Downstream effect
Suppression of apoptosis, mitochondrial stabilization, reduced oxidative stress, preservation of germ cells and neurons under stressZhu 2022Lue 2021Velentza 2024
Membrane permeabilization, cytokine induction, autophagy, phagosome-lysosome fusion, chemotaxisAhmad 2026Zhang 2026
Feedback intact?
Not applicable — peptide acts as anti-apoptotic signal, not hormonal axis
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Origin
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
Endogenous human cathelicidin (37-AA fragment, residues 134–170 of hCAP-18)
Antibody development
Not reported in animal models
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02Dosage Protocols
Parameter
Humanin
LL-37
Standard experimental dose (HNG)
4 mg/kg IP (rat)
Most common dose in rodent models.
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Ex vivo bone culture
1 µg/mL
Protective against venetoclax-induced bone growth retardation.
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Frequency
Daily (IP)
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Duration
8–12 weeks in animal studies
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Evidence basis
Animal models (rat, mouse)Huang 2025El 2022Velentza 2024
In vitro, animal models, human observational
Human data
None — no clinical trials reported
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Analog (HNG)
Gly[14]-humanin — more potent variant
Substitution at position 14 enhances cytoprotective activity.
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Endogenous expression
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Constitutive in neutrophils, epithelial tissues
Upregulated during infection and inflammation.Pinheiro 2026
Exogenous (experimental)
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Dose varies by study; antimalarial ~10–50 μM in vitro
No FDA-approved exogenous formulation.
03Metabolic / Fat Loss Evidence
Parameter
Humanin
LL-37
Direct fat loss evidence
None
—
Mechanism overlap
Mitochondrial health may indirectly influence metabolic efficiency, but no quantified effect
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04Side Effects & Safety
Parameter
Humanin
LL-37
Animal model safety
Well-tolerated in rat and mouse studies at 4 mg/kg for 8–12 weeks
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Human safety data
None — no clinical trials
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Theoretical fibrillation risk
Induces amyloid-like fibrillation of Bax/BID. Long-term sequelae unknown.
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Injection site reaction
Not reported in animal studies (IP route)
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Reproductive safety
Protective in POI model (cyclophosphamide-induced), no adverse effects on fertility notedHuang 2025
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Cytotoxicity (high dose)
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Membrane disruption in host cells at supraphysiological concentrations
Pro-inflammatory signaling
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Can exacerbate inflammation in certain contexts (context-dependent)Pinheiro 2026
Theoretical cancer risk
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Immunomodulatory roles in tumor microenvironment under investigation
Absolute Contraindications
Humanin
- ·Unknown — no human data
LL-37
—Relative Contraindications
Humanin
- ·Active malignancy (theoretical risk of anti-apoptotic effect on tumour cells)
LL-37
- ·Active autoimmune disease (theoretical immune dysregulation)
05Administration Protocol
Parameter
Humanin
LL-37
1. Route (experimental)
Intraperitoneal (IP) in animal models. Subcutaneous route untested. No human protocols exist.
LL-37 is constitutively expressed in neutrophils and epithelial cells, cleaved from hCAP-18 by proteinase-3 at sites of infection or inflammation.
2. Reconstitution
Synthetic peptide reconstituted in sterile saline or PBS. No commercial formulation available.
Synthetic LL-37 and derivatives (e.g., SAMP-12aa) tested in vitro and animal models. Administered via topical, intraperitoneal, or intravenous routes in research settings.
3. Timing
Daily administration in animal studies. Optimal timing not characterized.
LL-37 is resistant to pepsin degradation at gastric pH. Synthetic short peptides designed to retain this stability while reducing toxicity.Lu 2026
4. Storage
Lyophilised powder: -20 °C. Reconstituted: 4 °C, use within 7 days. Avoid freeze-thaw cycles.
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5. Human use
No FDA approval, no IND, no clinical trials. Experimental research tool only.
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06Stack Synergy
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
LL-37
— no documented stacks