Side-by-side · Research reference

CortagenvsHumanin

Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.

AAnimal-MechanisticHUMAN-REVIEWED11/35 cited

BAnimal-StrongHUMAN-REVIEWED14/52 cited

Cortagen

Bioregulatory Tetrapeptide · Khavinson-School

TetrapeptideStructure

↓ LPO productsAntioxidant effectKozina 2007

AnimalEvidence level

Injectable · Animal models

Humanin

Mitochondrial-Derived Peptide · Cytoprotective

24-AAPeptide lengthZhu 2022

mtDNAEncoded originZhu 2022 Shahzaib 2026

Bax/BimPrimary targetZhu 2022 Morris 2021

SQ · Experimental

01Mechanism of Action

Parameter

Cortagen

Humanin

Primary target

Cerebral cortex tissue — molecular targets under investigation

Intracellular: Bax, Bim, tBid (pro-apoptotic Bcl-2 family). Extracellular: FPRL1/2 G-protein-coupled receptorsZhu 2022 Lue 2021

Pathway

Antioxidant pathway modulation — suppression of LPO cascade, reduction of protein oxidative modificationKozina 2007

Humanin binds Bax/Bim → inhibits mitochondrial outer membrane permeabilization (MOMP) → blocks cytochrome c release → prevents caspase activation → cell survival

Downstream effect

Decreased lipid peroxidation products, reduced oxidative protein damage, altered gene expression in cardiac tissueKozina 2007 Anisimov 2004

Suppression of apoptosis, mitochondrial stabilization, reduced oxidative stress, preservation of germ cells and neurons under stressZhu 2022 Lue 2021 Velentza 2024

Feedback intact?

—

Not applicable — peptide acts as anti-apoptotic signal, not hormonal axis

Origin

Synthetic tetrapeptide derived from amino acid analysis of natural brain cortex peptide preparation CortexinAnisimov 2004

Encoded by short open reading frame in mitochondrial 16S rRNA gene (MTRNR2). 24-28 amino acids. 13 homologous variants (MTRNR2L1-L13) identified.Zhu 2022 Shahzaib 2026

Antibody development

—

Not reported in animal models

02Dosage Protocols

Parameter

Cortagen

Humanin

Animal model dose (rat)

Injection protocol (dose not specified in abstracts)

Multiple injections over study period.

—

Avian model dose (chicken)

40-day injection courseKuznik 2008

Compared to epithalon in hypophysectomized and aged birds.

—

Human peripheral nerve study

Therapeutic course (protocol details not provided)

Posttraumatic recovery context — reference cited but not detailed.

—

Evidence basis

Animal mechanistic studies

Animal models (rat, mouse)Huang 2025 El 2022 Velentza 2024

Route

Injectable (inferred from animal protocols)

—

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.

Frequency

—

Daily (IP)

Duration

—

8–12 weeks in animal studies

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

Cortagen

Humanin

Direct fat loss evidence

—

None

Mechanism overlap

—

Mitochondrial health may indirectly influence metabolic efficiency, but no quantified effect

04Side Effects & Safety

Parameter

Cortagen

Humanin

Antioxidant suppression

Suppression of antioxidant activity noted alongside LPO reductionKozina 2007

Mechanism unclear — possible homeostatic adaptation.

—

Immune/hemostasis effects

No effect on immunity or hemostasis parameters in avian hypophysectomy model (unlike epithalon)Kuznik 2008

Epithalon reversed deficits; cortagen did not.

—

Human safety data

No adverse events reported in peripheral nerve recovery context

Limited detail in available abstracts.

None — no clinical trials

Animal model safety

—

Well-tolerated in rat and mouse studies at 4 mg/kg for 8–12 weeks

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

Cortagen

—

Humanin

·Unknown — no human data

Relative Contraindications

Cortagen

—

Humanin

·Active malignancy (theoretical risk of anti-apoptotic effect on tumour cells)

05Administration Protocol

Parameter

Cortagen

Humanin

1. Preparation

Reconstitute lyophilised peptide with bacteriostatic water per supplier protocol. Exact volumes depend on concentration supplied.

Intraperitoneal (IP) in animal models. Subcutaneous route untested. No human protocols exist.

2. Injection site

Subcutaneous injection typical for bioregulatory peptides — abdomen or thigh. Rotate sites.

Synthetic peptide reconstituted in sterile saline or PBS. No commercial formulation available.

3. Timing

Animal protocols used repeated dosing over weeks. Human timing not established — evening administration common in Khavinson tradition.

Daily administration in animal studies. Optimal timing not characterized.

4. Storage

Lyophilised: refrigerate or freeze per supplier. Reconstituted: refrigerate 2–8 °C, use within guideline window.

Lyophilised powder: -20 °C. Reconstituted: 4 °C, use within 7 days. Avoid freeze-thaw cycles.

5. Human use

—

No FDA approval, no IND, no clinical trials. Experimental research tool only.

06Stack Synergy

Cortagen

— no documented stacks

Humanin

+ MOTS-c

Multi-pathway

View MOTS-c →

Both 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