Side-by-side · Research reference

IGF-1 LR3vsPE 22-28

Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.

AAnimal-StrongHUMAN-REVIEWED10/58 cited

BAnimal-StrongHUMAN-REVIEWED16/47 cited

IGF-1 LR3

IGF-1 Analogue · Research

3–10×Potency vs IGF-I

Low IGFBPBinding affinity

ResearchStatus

Research only · SQ typical in animal models

PE 22-28

TREK-1 Antagonist · Pre-Clinical

0.12 nMTREK-1 IC50Djillani 2017

7 AAPeptide lengthDjillani 2017

AnimalEvidence stage

IP · SQ · Once Daily (animal models)Djillani 2017 Pietri 2019

01Mechanism of Action

Parameter

IGF-1 LR3

PE 22-28

Primary target

IGF-1 receptor (IGF-1R)McTavish 2009

TREK-1 two-pore-domain potassium channelDjillani 2017 Ma 2020

Pathway

IGF-1R → IRS-1 → PI3K/Akt → Cell proliferation, protein synthesis, anti-apoptosisMuhlbradt 2009

TREK-1 channel blockade → Neuronal membrane depolarisation → Enhanced hippocampal excitability → Increased neuroplasticity

Downstream effect

Enhanced cell proliferation, muscle anabolism, inhibition of apoptosis, increased telomerase activity

Antidepressant-like activity in forced swim test and tail suspension test; reduced A1-like reactive astrocyte activation; neuroprotection via NF-κB pathway modulationDjillani 2017 Cong 2023 Wu 2021

Feedback intact?

No — exogenous IGF analogue bypasses GH-mediated regulation

N/A — direct ion channel blockade; not receptor-mediated endocrine axis

Origin

Synthetic 83-AA analogue: 13-AA N-terminal extension + Arg substitution at position 3

Synthetic truncation of spadin (PE 12-28), itself derived from the sortilin propeptide C-terminus. Residues 22-28: Val-Val-Arg-Gly-Trp-Leu-Arg.Djillani 2017 Mazella 2018

Antibody development

—

Not reported in animal studies

02Dosage Protocols

Parameter

IGF-1 LR3

PE 22-28

Research dose (animal models)

Variable by protocol and species

In vivo murine atherosclerosis studies used sustained delivery.

—

In vitro typical concentration

10–1000 ng/mLThomas 2007

Dose-dependent effects on follicle growth and estradiol production.

—

Half-maximal stimulation

0.6 nM LR3 vs 1.5 nM native IGF-1Price 2004

2.5-fold greater potency in lung fibroblast proliferation.

—

Evidence basis

Animal / in vitro only

Multiple rodent RCTs; behavioral + electrophysiology endpointsDjillani 2017 Qi 2018 Wu 2021

Human use

Not FDA-approved; no published human trials

—

Animal dose (antidepressant)

—

0.3–3 µg/kg IP

Effective in forced swim test, tail suspension test, CUMS models.

Animal dose (neuroprotection)

—

0.03 µg/kg IPPietri 2019

Low-dose TREK-1 activation post-stroke for 7 days, then high-dose blockade.

Frequency

—

Once daily

Sustained antidepressant effect over 7+ days.

Onset (animal)

—

Within hours (acute); full effect 4–7 days

Duration (animal)

—

7–28 days testedQi 2018 Pietri 2019

Comparison to fluoxetine

—

PE 22-28 outperforms fluoxetine in CUMS-sensitive rats by day 7

Chronic administration shows superior long-term efficacy.

Human equivalent (extrapolated)

—

Not established — no clinical trials

Allometric scaling from rodent data unavailable.

03Metabolic / Fat Loss Evidence

Parameter

IGF-1 LR3

PE 22-28

Mechanism

IGF-1R activation → lipolytic signaling; secondary to anabolic effects

—

Direct lipolytic evidence

Minimal — primarily anabolic/anti-apoptotic in literature

—

Atherosclerotic plaque effects

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

IGF-1 LR3

PE 22-28

Hypoglycemia risk

Theoretical — IGF-1 analogues can lower blood glucose

—

Excessive cell proliferation

Mitogenic signaling; theoretical tumor promotion risk

—

Telomerase activation

2–10-fold increase in prostate cancer cells (PC-3, DU-145, LAPC-4)Wetterau 2003

Critically involved in cancer cell immortalization.

—

Oocyte degeneration

Increased oocyte degeneration at high doses (≥1000 ng/mL) in bovine folliclesThomas 2007

—

Unregulated anabolism

Bypasses physiological GH/IGF-1 feedback; no pulsatility control

—

Unknown human safety profile

No published human trials; safety data absent

—

Toxicity (animal)

—

No adverse effects reported at therapeutic doses

Cardiovascular (theoretical)

—

TREK-1 expressed in cardiac tissue; arrhythmia risk unclear

Weight change

—

Not reported in animal studies

Neurological

—

No seizures or behavioral abnormalities noted

Long-term safety

—

Unknown — longest animal study 28 days

Absolute Contraindications

IGF-1 LR3

·Active malignancy or history of cancer
·Not approved for human use

PE 22-28

·Human use — no clinical safety data available

Relative Contraindications

IGF-1 LR3

·Diabetes or glucose intolerance
·Family history of cancer

PE 22-28

·Cardiac arrhythmia or channelopathy (theoretical TREK-1 cardiac role)

05Administration Protocol

Parameter

IGF-1 LR3

PE 22-28

1. Research use only

IGF-1 LR3 is not FDA-approved for human use. All administration data derives from animal or in vitro studies.

Dissolved in sterile saline or vehicle. Intraperitoneal injection, 0.3–3 µg/kg body weight. Once daily administration in rodent behavioral studies.

2. Typical research route

Subcutaneous or intraperitoneal injection in animal models. In vitro: added directly to culture medium at concentrations of 10–1000 ng/mL.Thomas 2007

Shorter peptide length (7 AA) confers improved plasma stability vs 17-AA spadin. Exact storage conditions not detailed in published protocols.Djillani 2017

3. Reconstitution (research)

Lyophilised powder reconstituted in sterile water or buffered saline per manufacturer protocol. Store at 2–8 °C after reconstitution.

Enhanced CNS bioavailability vs full spadin, likely due to smaller size. Mechanism (passive diffusion vs active transport) not fully characterized.

4. Stability

Enhanced stability vs native IGF-1 due to reduced IGFBP binding; exact half-life in vivo not fully characterized in humans.

Not established — peptide synthesis methods for research use only. No pharmaceutical-grade formulation available.

06Stack Synergy

IGF-1 LR3

+ GHRP-6

Multi-pathway

View GHRP-6 →

GHRP-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-pathway

View Ipamorelin →

Ipamorelin (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)

PE 22-28

— no documented stacks