Side-by-side · Research reference

HumaninvsThymosin α-1

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

BPhase 3HUMAN-REVIEWED8/39 cited

Humanin

Mitochondrial-Derived Peptide · Cytoprotective

24-AAPeptide lengthZhu 2022

mtDNAEncoded originZhu 2022 Shahzaib 2026

Bax/BimPrimary targetZhu 2022 Morris 2021

SQ · Experimental

Thymosin α-1

Immune modulator · Approved (some countries)

1.6 mgPer doseIyer 2007

Phase 3Evidence levelIyer 2007 Camerini 2001

~2 hrHalf-life

SQ · 2× weekly · 6+ months for chronic indications

01Mechanism of Action

Parameter

Humanin

Thymosin α-1

Primary target

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

Toll-like receptor 9 (TLR9) + T-cell maturation pathwayCamerini 2001

Pathway

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

TLR9 activation → ↑ IFN-α + IL-2 + IFN-γ → enhanced T-cell function + dendritic cell maturationIyer 2007

Downstream effect

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

Restored T-cell function, improved viral clearance, anti-tumour adjuvant effectsIyer 2007

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 28-AA peptide identical to natural Tα-1 isolated from thymus extractCamerini 2001

Antibody development

Not reported in animal models

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02Dosage Protocols

Parameter

Humanin

Thymosin α-1

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)

2× weekly (Mon/Thu typical)

Duration

8–12 weeks in animal studies

6–12 months for chronic indications

Evidence basis

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

Phase 3 + approved (35+ countries as Zadaxin)Iyer 2007

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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Standard dose (HBV/HCV)

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1.6 mg SQ 2× weekly × 6–12 monthsIyer 2007

Lower / starter dose

—

0.8 mg per injection

Reconstitution

—

Sterile water for injection per vial label

Timing

—

No specific time

Half-life

—

~2 hours plasma; tissue effect days

03Metabolic / Fat Loss Evidence

Parameter

Humanin

Thymosin α-1

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

Thymosin α-1

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)

Erythema, mild discomfort

Reproductive safety

Protective in POI model (cyclophosphamide-induced), no adverse effects on fertility notedHuang 2025

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GI symptoms

—

Rare nausea

Fatigue

—

Common during initial weeks

Fever / flu-like

—

Mild interferon-like response possible

Autoimmune

—

Theoretical risk; caution in active autoimmune disease

Cancer risk

—

No signal — used as adjuvant in oncology

Pregnancy / OB

—

Avoid

Absolute Contraindications

Humanin

·Unknown — no human data

Thymosin α-1

·Pregnancy / breastfeeding
·Hypersensitivity to peptide
·Concurrent immunosuppressant therapy (transplant patients)

Relative Contraindications

Humanin

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

Thymosin α-1

·Active autoimmune disease
·Severe immunocompromised state without supervision

05Administration Protocol

Parameter

Humanin

Thymosin α-1

1. Route (experimental)

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

Add 1 mL sterile water per 1.6 mg vial → 1.6 mg/mL.

2. Reconstitution

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

SQ — abdomen, thigh, or upper arm. Rotate sites.

3. Timing

Daily administration in animal studies. Optimal timing not characterized.

2× weekly, e.g. Monday + Thursday.

4. Storage

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

Lyophilised: refrigerate. Reconstituted: refrigerate, use within 24 h.

5. Human use

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

27–31G, 4–8 mm insulin syringe.

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

Thymosin α-1

— no documented stacks