Side-by-side · Research reference
HumaninvsIGF-1 LR3
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-StrongHUMAN-REVIEWED10/58 cited
Humanin
Mitochondrial-Derived Peptide · Cytoprotective
SQ · Experimental
IGF-1 LR3
IGF-1 Analogue · Research
3–10×Potency vs IGF-I
Low IGFBPBinding affinity
ResearchStatus
Research only · SQ typical in animal models
01Mechanism of Action
Parameter
Humanin
IGF-1 LR3
Primary target
Intracellular: Bax, Bim, tBid (pro-apoptotic Bcl-2 family). Extracellular: FPRL1/2 G-protein-coupled receptorsZhu 2022Lue 2021
IGF-1 receptor (IGF-1R)McTavish 2009
Pathway
Humanin binds Bax/Bim → inhibits mitochondrial outer membrane permeabilization (MOMP) → blocks cytochrome c release → prevents caspase activation → cell survival
IGF-1R → IRS-1 → PI3K/Akt → Cell proliferation, protein synthesis, anti-apoptosisMuhlbradt 2009
Downstream effect
Suppression of apoptosis, mitochondrial stabilization, reduced oxidative stress, preservation of germ cells and neurons under stressZhu 2022Lue 2021Velentza 2024
Enhanced cell proliferation, muscle anabolism, inhibition of apoptosis, increased telomerase activity
Feedback intact?
Not applicable — peptide acts as anti-apoptotic signal, not hormonal axis
No — exogenous IGF analogue bypasses GH-mediated regulation
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
Synthetic 83-AA analogue: 13-AA N-terminal extension + Arg substitution at position 3
Antibody development
Not reported in animal models
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02Dosage Protocols
Parameter
Humanin
IGF-1 LR3
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)
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Duration
8–12 weeks in animal studies
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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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Research dose (animal models)
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Variable by protocol and species
In vivo murine atherosclerosis studies used sustained delivery.
In vitro typical concentration
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10–1000 ng/mLThomas 2007
Dose-dependent effects on follicle growth and estradiol production.
Half-maximal stimulation
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0.6 nM LR3 vs 1.5 nM native IGF-1Price 2004
2.5-fold greater potency in lung fibroblast proliferation.
Human use
—
Not FDA-approved; no published human trials
03Metabolic / Fat Loss Evidence
Parameter
Humanin
IGF-1 LR3
Direct fat loss evidence
None
—
Mechanism overlap
Mitochondrial health may indirectly influence metabolic efficiency, but no quantified effect
—
Mechanism
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IGF-1R activation → lipolytic signaling; secondary to anabolic effects
Direct lipolytic evidence
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Minimal — primarily anabolic/anti-apoptotic in literature
Atherosclerotic plaque effects
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Reduced stenosis and core size in ApoE-KO micevon 2011
Plaque stabilization via vSMC phenotype modulation, not direct fat loss.
Human data
—
None published
04Side Effects & Safety
Parameter
Humanin
IGF-1 LR3
Animal model safety
Well-tolerated in rat and mouse studies at 4 mg/kg for 8–12 weeks
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Human safety data
None — no clinical trials
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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
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Hypoglycemia risk
—
Theoretical — IGF-1 analogues can lower blood glucose
Excessive cell proliferation
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Mitogenic signaling; theoretical tumor promotion risk
Telomerase activation
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2–10-fold increase in prostate cancer cells (PC-3, DU-145, LAPC-4)Wetterau 2003
Critically involved in cancer cell immortalization.
Oocyte degeneration
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Increased oocyte degeneration at high doses (≥1000 ng/mL) in bovine folliclesThomas 2007
Unregulated anabolism
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Bypasses physiological GH/IGF-1 feedback; no pulsatility control
Unknown human safety profile
—
No published human trials; safety data absent
Absolute Contraindications
Humanin
- ·Unknown — no human data
IGF-1 LR3
- ·Active malignancy or history of cancer
- ·Not approved for human use
Relative Contraindications
Humanin
- ·Active malignancy (theoretical risk of anti-apoptotic effect on tumour cells)
IGF-1 LR3
- ·Diabetes or glucose intolerance
- ·Family history of cancer
05Administration Protocol
Parameter
Humanin
IGF-1 LR3
1. Route (experimental)
Intraperitoneal (IP) in animal models. Subcutaneous route untested. No human protocols exist.
IGF-1 LR3 is not FDA-approved for human use. All administration data derives from animal or in vitro studies.
2. Reconstitution
Synthetic peptide reconstituted in sterile saline or PBS. No commercial formulation available.
Subcutaneous or intraperitoneal injection in animal models. In vitro: added directly to culture medium at concentrations of 10–1000 ng/mL.Thomas 2007
3. Timing
Daily administration in animal studies. Optimal timing not characterized.
Lyophilised powder reconstituted in sterile water or buffered saline per manufacturer protocol. Store at 2–8 °C after reconstitution.
4. Storage
Lyophilised powder: -20 °C. Reconstituted: 4 °C, use within 7 days. Avoid freeze-thaw cycles.
Enhanced stability vs native IGF-1 due to reduced IGFBP binding; exact half-life in vivo not fully characterized in humans.
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-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
IGF-1 LR3
+ GHRP-6
Multi-pathwayGHRP-6 stimulates endogenous GH release, which drives hepatic IGF-1 synthesis. IGF-1 LR3 provides exogenous, IGFBP-resistant IGF signaling. Combining upstream GH stimulation with downstream IGF receptor activation creates a dual-pathway anabolic effect. However, this bypasses natural feedback and carries compounded mitogenic risk.
- GHRP-6
- 100–200 mcg SQ · 2–3× daily
- IGF-1 LR3
- Research doses variable · post-workout typical in animal models
- Note
- Research context only — no human protocols exist
- Primary benefit
- Theoretical maximal anabolic signaling (GH + IGF axes)
+ Ipamorelin
Multi-pathwayIpamorelin (selective GHRP) stimulates pulsatile GH release without cortisol/prolactin elevation. IGF-1 LR3 directly activates IGF-1R independent of GH. This stack targets both upstream (GH secretion) and downstream (IGF receptor) nodes but eliminates physiological feedback, raising safety concerns around unchecked proliferation.
- Ipamorelin
- 200–300 mcg SQ · evening
- IGF-1 LR3
- Research doses only · timing variable
- Caution
- No human data; animal/in vitro only
- Primary benefit
- Dual-axis anabolic signaling (theoretical)