Side-by-side · Research reference

HumaninvsSemax

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-MechanisticAUTO-DRAFTED12/39 cited

Humanin

Mitochondrial-Derived Peptide · Cytoprotective

24-AAPeptide lengthZhu 2022

mtDNAEncoded originZhu 2022 Shahzaib 2026

Bax/BimPrimary targetZhu 2022 Morris 2021

SQ · Experimental

Semax

Cognitive enhancer · Russian Pharma

200–600 mcg/doseIntranasalKaplan 2017

HumanMechanisticKaplan 2017

~30 minOnset

Intranasal · 2–3×/day during cognitive demand

01Mechanism of Action

Parameter

Humanin

Semax

Primary target

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

BDNF / NGF expression + monoamine modulationKaplan 2017

Pathway

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

↑ BDNF + NGF synthesis + 5-HT modulation → neuroplasticity + anxiolysis + cognitive enhancementKaplan 2017

Downstream effect

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

Improved memory + attention; reduced anxiety; neuroprotection in ischemiaKaplan 2017

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 2022 Shahzaib 2026

Synthetic 7-AA peptide derived from ACTH(4-7) with C-terminal Pro-Gly-Pro stabilising tailKaplan 2017

Antibody development

Not reported in animal models

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02Dosage Protocols

Parameter

Humanin

Semax

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)

2–3× per day during cognitive demand

Duration

8–12 weeks in animal studies

10–14 day cycles, repeated PRN

Evidence basis

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

Human-mechanistic + Russian clinicalKaplan 2017

Human data

None — no clinical trials reported

—

Analog (HNG)

Gly[14]-humanin — more potent variant

Substitution at position 14 enhances cytoprotective activity.

—

Standard dose

—

200–600 mcg / dose intranasalKaplan 2017

Lower / starter dose

—

100 mcg / dose

Reconstitution

—

Pre-formulated nasal spray (commercial); research vial: bacteriostatic water

Timing

—

Morning + early afternoon

Half-life

—

Short plasma; CNS effect lasts ~3–6 hr

03Metabolic / Fat Loss Evidence

Parameter

Humanin

Semax

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

Semax

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.

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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

—

Nasal irritation

—

Mild burning or congestion (transient)

Sleep disruption

—

Late-day dosing may interfere with sleep

Headache

—

Uncommon, transient

Long-term safety

—

Limited Western RCT data

Pregnancy / OB

—

Avoid

Absolute Contraindications

Humanin

·Unknown — no human data

Semax

·Pregnancy / breastfeeding

Relative Contraindications

Humanin

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

Semax

·Active psychiatric instability
·Concurrent strong stimulants

05Administration Protocol

Parameter

Humanin

Semax

1. Route (experimental)

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

Pre-formulated nasal spray (commercial) or research vial reconstituted with bacteriostatic water.

2. Reconstitution

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

Intranasal — 2–3 sprays per nostril per dose. Tilt head slightly back.

3. Timing

Daily administration in animal studies. Optimal timing not characterized.

Morning + early afternoon. Avoid evening (sleep disruption).

4. Storage

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

Refrigerate after reconstitution; light-protected.

5. Human use

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

Cycle on/off to avoid neurochemical adaptation.

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

Semax

+ Selank

Moderate

View Selank →

Semax (cognitive enhancer, BDNF/NGF) and Selank (anxiolytic + immune) form the canonical Russian "neuro stack" — both intranasal peptide bioregulators with complementary axes. Semax for cognitive demand; Selank for stress mitigation.

Semax: 200–600 mcg intranasal · morning + afternoon
Selank: 150–300 mcg intranasal · midday + early evening
Primary benefit: Cognitive enhancement + stress mitigation

Kaplan 2017 Zaderej 2014