Side-by-side · Research reference
IGF-1 LR3vsSS-31
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
BPhase 3HUMAN-REVIEWED9/43 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
SS-31
Cardiolipin-binding · Mitochondrial protective
SQ · Abdomen · Once daily
01Mechanism of Action
Parameter
IGF-1 LR3
SS-31
Primary target
IGF-1 receptor (IGF-1R)McTavish 2009
Cardiolipin in inner mitochondrial membraneSzeto 2014
Pathway
IGF-1R → IRS-1 → PI3K/Akt → Cell proliferation, protein synthesis, anti-apoptosisMuhlbradt 2009
Cardiolipin binding → cristae stabilisation → ETC integrity → reduced ROS + preserved ATP synthesisSzeto 2014Szilagyi 2009
Downstream effect
Enhanced cell proliferation, muscle anabolism, inhibition of apoptosis, increased telomerase activity
Mitochondrial bioenergetic preservation; cardio-, neuro-, and reno-protective effects in animal + clinical studiesSzeto 2014
Feedback intact?
No — exogenous IGF analogue bypasses GH-mediated regulation
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Origin
Synthetic 83-AA analogue: 13-AA N-terminal extension + Arg substitution at position 3
Synthetic tetrapeptide D-Arg-Dmt-Lys-Phe-NH₂; cell-permeable, mitochondrial-selectiveSzeto 2014
Antibody development
—
—
02Dosage Protocols
Parameter
IGF-1 LR3
SS-31
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 Phase 3 trials (Barth, AMD, ischemia-reperfusion)Szeto 2014Szilagyi 2009
Human use
Not FDA-approved; no published human trials
—
Standard dose
—
40 mg / day SQ (clinical trials)Szeto 2014
Anecdotal community range 5-10 mg/day. Phase 3 trials use 40 mg.
Frequency
—
Once daily
Lower / starter dose
—
5 mg / day (anecdotal)
Duration
—
Indefinite for mitochondrial disease; cycled for healthspan use
Reconstitution
—
Bacteriostatic water
Timing
—
Morning fasted preferred; pre-workout for exercise-induced mitochondrial stress
Half-life
—
~3 h plasma; tissue uptake longer
03Metabolic / Fat Loss Evidence
Parameter
IGF-1 LR3
SS-31
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
SS-31
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
—
Injection site reaction
—
Erythema, mild pruritus
GI symptoms
—
Nausea (uncommon)
Headache
—
Reported in some Phase 3 trials
Cardiovascular
—
Cardio-protective in studies; no signal of harm
Pregnancy / OB
—
Avoid — insufficient data
Absolute Contraindications
IGF-1 LR3
- ·Active malignancy or history of cancer
- ·Not approved for human use
SS-31
- ·Pregnancy / breastfeeding
- ·Hypersensitivity to peptide
Relative Contraindications
IGF-1 LR3
- ·Diabetes or glucose intolerance
- ·Family history of cancer
SS-31
- ·None established
05Administration Protocol
Parameter
IGF-1 LR3
SS-31
1. Research use only
IGF-1 LR3 is not FDA-approved for human use. All administration data derives from animal or in vitro studies.
Add bacteriostatic water per label. Light-protected handling.
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
SQ — abdomen or thigh. Rotate sites.
3. Reconstitution (research)
Lyophilised powder reconstituted in sterile water or buffered saline per manufacturer protocol. Store at 2–8 °C after reconstitution.
Morning fasted; pre-workout for exercise-augmented mitochondrial stress.
4. Stability
Enhanced stability vs native IGF-1 due to reduced IGFBP binding; exact half-life in vivo not fully characterized in humans.
Lyophilised: refrigerate, light-protected. Reconstituted: refrigerate ≤30 days.
5. Needle
—
29–31G, 4–8 mm insulin syringe.
06Stack Synergy
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)
SS-31
+ MOTS-c
ModerateSS-31 and MOTS-c address mitochondrial decline through complementary axes. SS-31 protects existing mitochondrial structure (cardiolipin binding, cristae stabilisation). MOTS-c upregulates AMPK/PGC-1α, triggering biogenesis of new mitochondria. Together they pair preservation with renewal — anecdotally favoured in healthspan and post-cardio-event recovery protocols.
- SS-31
- 5–10 mg SQ · daily morning
- MOTS-c
- 5 mg SQ · 2× per week pre-workout
- Primary benefit
- Mitochondrial preservation + biogenesis