Side-by-side · Research reference
HumaninvsTB-500
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 2HUMAN-REVIEWED8/46 cited
Humanin
Mitochondrial-Derived Peptide · Cytoprotective
SQ · Experimental
TB-500
Thymosin β4 fragment · Healing
SQ or IM · Multiple sites · 2–3×/week
01Mechanism of Action
Parameter
Humanin
TB-500
Primary target
Intracellular: Bax, Bim, tBid (pro-apoptotic Bcl-2 family). Extracellular: FPRL1/2 G-protein-coupled receptorsZhu 2022Lue 2021
G-actin (sequestering) + cell-surface integrinsGoldstein 2012
Pathway
Humanin binds Bax/Bim → inhibits mitochondrial outer membrane permeabilization (MOMP) → blocks cytochrome c release → prevents caspase activation → cell survival
Actin remodelling → cell migration; integrin-linked signaling → angiogenesis; anti-inflammatory cytokine modulationGoldstein 2012Malinda 1999
Downstream effect
Suppression of apoptosis, mitochondrial stabilization, reduced oxidative stress, preservation of germ cells and neurons under stressZhu 2022Lue 2021Velentza 2024
Accelerated wound healing, endothelial migration, hair follicle regeneration, cardiac repair (preclinical)Goldstein 2012
Feedback intact?
Not applicable — peptide acts as anti-apoptotic signal, not hormonal axis
Endogenous protein at baseline; supplementation amplifies
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
17-AA active fragment of endogenous 43-AA thymosin β4 (TMSB4X gene)Goldstein 2012
Antibody development
Not reported in animal models
—
02Dosage Protocols
Parameter
Humanin
TB-500
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)
2× per week (loading); then 1× per week (maintenance)
Duration
8–12 weeks in animal studies
4–8 weeks loading; longer maintenance for chronic injury
Evidence basis
Animal models (rat, mouse)Huang 2025El 2022Velentza 2024
Animal-strong + Phase 2 dermal/ocular trialsGoldstein 2012
Human data
None — no clinical trials reported
—
Analog (HNG)
Gly[14]-humanin — more potent variant
Substitution at position 14 enhances cytoprotective activity.
—
Standard dose
—
2 mg per injectionGoldstein 2012
Anecdotal community range; clinical Phase 2 trials used 70–840 mcg/kg IV.
Lower / starter dose
—
1 mg per injection
Reconstitution
—
Bacteriostatic water, 1–2 mL per 5 mg vial
Timing
—
Evening or pre-rest preferred (anecdotal)
Half-life
—
~2 hours (estimated; tissue uptake longer)
03Metabolic / Fat Loss Evidence
Parameter
Humanin
TB-500
Direct fat loss evidence
None
—
Mechanism overlap
Mitochondrial health may indirectly influence metabolic efficiency, but no quantified effect
—
04Side Effects & Safety
Parameter
Humanin
TB-500
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)
Mild erythema, transient pain
Reproductive safety
Protective in POI model (cyclophosphamide-induced), no adverse effects on fertility notedHuang 2025
—
GI symptoms
—
Rare nausea (anecdotal)
Cancer risk
—
Theoretical via angiogenesis pathway
Lethargy / fatigue
—
Reported anecdotally during loading phase
Antibody formation
—
No data (no long-term human trials)
Pregnancy / OB
—
Avoid
Long-term safety
—
Unknown beyond Phase 2
Absolute Contraindications
Humanin
- ·Unknown — no human data
TB-500
- ·Active malignancy (theoretical angiogenesis concern)
- ·Pregnancy / breastfeeding
Relative Contraindications
Humanin
- ·Active malignancy (theoretical risk of anti-apoptotic effect on tumour cells)
TB-500
- ·Cancer history
- ·Concurrent VEGF inhibitor therapy
05Administration Protocol
Parameter
Humanin
TB-500
1. Route (experimental)
Intraperitoneal (IP) in animal models. Subcutaneous route untested. No human protocols exist.
Add 1–2 mL bacteriostatic water to 5 mg vial → 2.5–5 mg/mL. Roll gently.
2. Reconstitution
Synthetic peptide reconstituted in sterile saline or PBS. No commercial formulation available.
SQ near injury site (preferred), or systemic SQ (abdomen). Rotate sites.
3. Timing
Daily administration in animal studies. Optimal timing not characterized.
Evening or pre-sleep is most common anecdotal timing.
4. Storage
Lyophilised powder: -20 °C. Reconstituted: 4 °C, use within 7 days. Avoid freeze-thaw cycles.
Lyophilised: room temp, light-protected. Reconstituted: refrigerate, ≤30 days.
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-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
TB-500
+ BPC-157
StrongTB-500 and BPC-157 cover complementary halves of tissue repair: BPC-157 upregulates VEGFR2-driven angiogenesis and fibroblast outgrowth; TB-500 sequesters G-actin to enable endothelial / epithelial migration. The anecdotal canonical "healing stack" — pairs especially well for tendon and ligament injuries.
- TB-500
- 2 mg SQ · 2× per week
- BPC-157
- 250–500 mcg SQ · daily
- Primary benefit
- Combined angiogenesis + cell migration for tendon/ligament/muscle repair