Side-by-side · Research reference

HumaninvsVesugen

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

BAnimal-MechanisticHUMAN-REVIEWED5/43 cited

Humanin

Mitochondrial-Derived Peptide · Cytoprotective

24-AAPeptide lengthZhu 2022

mtDNAEncoded originZhu 2022 Shahzaib 2026

Bax/BimPrimary targetZhu 2022 Morris 2021

SQ · Experimental

Vesugen

Bioregulatory Tripeptide · Vascular Endothelium

3 AATripeptide

Endothelin-1 ↓Atherosclerotic tissue

Ki-67 ↑Aged endothelium

SQ / IM · Protocol varies

01Mechanism of Action

Parameter

Humanin

Vesugen

Primary target

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

Vascular endothelial cell nucleus — MKI67 gene promoter

Pathway

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

KED → MKI67 promoter interaction (CATC binding motif -14 to +12 bp) → Ki-67 proliferation protein ↑

Downstream effect

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

Normalised endothelin-1 expression in atherosclerotic/restenotic endothelium, restored connexin expression for cell-cell communication, enhanced proliferative capacity in senescent endothelial culturesKozlov 2016 Khavinson 2014

Feedback intact?

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

Not applicable — does not operate via hormone axis

Origin

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

Khavinson bioregulatory peptide school — designed as tissue-specific (vascular) cytomodulator

Antibody development

Not reported in animal models

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02Dosage Protocols

Parameter

Humanin

Vesugen

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)

Not specified in available literature

Duration

8–12 weeks in animal studies

Case series report treatment courses in elderly arterial insufficiency

Evidence basis

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

Animal models (atherosclerosis, restenosis, aging) · Russian case series

Human data

None — no clinical trials reported

—

Analog (HNG)

Gly[14]-humanin — more potent variant

Substitution at position 14 enhances cytoprotective activity.

—

Standard dose (reported)

—

Not standardised — Russian clinical case series

Protocols vary; no FDA-approved regimen.

Route

—

Subcutaneous or intramuscular

Half-life

—

Not reported

Tripeptides typically cleared rapidly.

03Metabolic / Fat Loss Evidence

Parameter

Humanin

Vesugen

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

Vesugen

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

—

Reported adverse events

—

None documented in available abstracts

Injection site

—

Assumed minimal — typical for small peptides

Long-term safety

—

Unknown — no long-term RCT data

Epigenetic mechanism risk

—

Theoretical concern: direct gene promoter interaction — proliferative effects in non-target tissues not characterised

Absolute Contraindications

Humanin

·Unknown — no human data

Vesugen

—

Relative Contraindications

Humanin

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

Vesugen

·Active malignancy — proliferative mechanism (Ki-67 upregulation) untested in oncologic context

05Administration Protocol

Parameter

Humanin

Vesugen

1. Route (experimental)

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

Lyophilised powder reconstituted with sterile water or bacteriostatic water per supplier protocol. No standardised formulation.

2. Reconstitution

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

Subcutaneous (abdomen, thigh) or intramuscular. Rotate sites if multi-dose protocol.

3. Timing

Daily administration in animal studies. Optimal timing not characterized.

No reported circadian or fasting requirement. Russian protocols typically integrated into geroprotective regimens.

4. Storage

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

Lyophilised: refrigerate 2–8 °C, light-protected. Reconstituted: use immediately or refrigerate per supplier guidance (typically <7 days).

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-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

Vesugen

+ Thymalin

Multi-pathway

View Thymalin →

Both from Khavinson bioregulatory school. Thymalin targets thymic/immune axis, Vesugen targets vascular endothelium. Rationale: multi-system geroprotection in elderly — immune senescence + vascular aging. Documented in Khavinson-tradition protocols combining tissue-specific peptides for poly-organ rejuvenation. No direct synergy study; combinatorial logic based on distinct target tissues.

Vesugen: Per protocol (SQ/IM)
Thymalin: Per protocol (SQ/IM)
Frequency: Sequential or concurrent per geroprotective protocol
Primary benefit: Multi-system age-related decline mitigation (vascular + immune)