Side-by-side · Research reference
HumaninvsPT-141
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
BFDA-ApprovedHUMAN-REVIEWED13/41 cited
Humanin
Mitochondrial-Derived Peptide · Cytoprotective
SQ · Experimental
PT-141
MC4R Agonist · FDA-Approved (HSDD)
SQ · Abdomen / thigh · ≥45 min before sex
01Mechanism of Action
Parameter
Humanin
PT-141
Primary target
Intracellular: Bax, Bim, tBid (pro-apoptotic Bcl-2 family). Extracellular: FPRL1/2 G-protein-coupled receptorsZhu 2022Lue 2021
Melanocortin-4 receptor (MC4R) in hypothalamusSimerly 2023VYLEESI (bremelanotide injecti 2019
Pathway
Humanin binds Bax/Bim → inhibits mitochondrial outer membrane permeabilization (MOMP) → blocks cytochrome c release → prevents caspase activation → cell survival
MC4R agonism in paraventricular nucleus → autonomic + neuroendocrine sexual arousal pathwaysSimerly 2023
Downstream effect
Suppression of apoptosis, mitochondrial stabilization, reduced oxidative stress, preservation of germ cells and neurons under stressZhu 2022Lue 2021Velentza 2024
Increased sexual desire and arousal; central rather than peripheral mechanismClayton 2015
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
Cyclic 7-AA peptide derived from α-MSH (agonist Ac-Nle-Asp-His-D-Phe-Arg-Trp-Lys-OH cyclic)VYLEESI (bremelanotide injecti 2019
Antibody development
Not reported in animal models
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02Dosage Protocols
Parameter
Humanin
PT-141
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.
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Frequency
Daily (IP)
PRN, max 8 doses / month
Duration
8–12 weeks in animal studies
PRN; reassess if no benefit after 8 doses
Evidence basis
Animal models (rat, mouse)Huang 2025El 2022Velentza 2024
FDA-approved (HSDD pre-menopausal women)VYLEESI (bremelanotide injecti 2019Clayton 2015
Human data
None — no clinical trials reported
—
Analog (HNG)
Gly[14]-humanin — more potent variant
Substitution at position 14 enhances cytoprotective activity.
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Standard dose
—
1.75 mg SQVYLEESI (bremelanotide injecti 2019
Single dose ≥45 min before anticipated sexual activity. Max 1 dose / 24 hr.
Lower / starter dose
—
1 mg (off-label)
Reconstitution
—
Pre-filled commercial pen (Vyleesi). Research vial: bacteriostatic water.
Timing
—
≥45 min before sexual activity
03Metabolic / Fat Loss Evidence
Parameter
Humanin
PT-141
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
PT-141
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)
Erythema, mild pain
Reproductive safety
Protective in POI model (cyclophosphamide-induced), no adverse effects on fertility notedHuang 2025
—
Flushing
—
Common, transient
Headache
—
Common
Hyperpigmentation (focal)
—
Rare focal skin darkening; reversible after discontinuationVYLEESI (bremelanotide injecti 2019
Hypertension (transient)
—
Mean ↑6 mmHg systolic peaking ~4 h post-dose; resolves within 12 hVYLEESI (bremelanotide injecti 2019
Pregnancy / OB
—
Contraindicated
Cardiovascular disease
—
Use caution; transient BP rise
Absolute Contraindications
Humanin
- ·Unknown — no human data
PT-141
- ·Uncontrolled hypertension
- ·Known cardiovascular disease (caution)
- ·Pregnancy
Relative Contraindications
Humanin
- ·Active malignancy (theoretical risk of anti-apoptotic effect on tumour cells)
PT-141
- ·Pre-existing hyperpigmentation disorders
- ·MC4R-pathway-dependent psychiatric conditions
05Administration Protocol
Parameter
Humanin
PT-141
1. Route (experimental)
Intraperitoneal (IP) in animal models. Subcutaneous route untested. No human protocols exist.
Vyleesi: pre-filled auto-injector. Research vial: 2 mL bacteriostatic water per 10 mg → 5 mg/mL.
2. Reconstitution
Synthetic peptide reconstituted in sterile saline or PBS. No commercial formulation available.
SQ — abdomen or thigh.
3. Timing
Daily administration in animal studies. Optimal timing not characterized.
≥45 min before sexual activity for peak effect. Effect persists ~6–8 h.
4. Storage
Lyophilised powder: -20 °C. Reconstituted: 4 °C, use within 7 days. Avoid freeze-thaw cycles.
Vyleesi: room temp ≤30 °C. Research vial: refrigerate after reconstitution.
5. Human use
No FDA approval, no IND, no clinical trials. Experimental research tool only.
Auto-injector (Vyleesi) or 29–31G, 4–8 mm insulin syringe.
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
PT-141
— no documented stacks