Side-by-side · Research reference

IpamorelinvsSS-31

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

APhase 1Reviewed21/57 cited

BPhase 3Reviewed9/43 cited

Ipamorelin

Selective GHRP · Ghrelin Mimetic

200–300 mcgPer doseRaun 1998

Phase 1Evidence levelRaun 1998 Sigalos 2018

~2 hrHalf-lifeRaun 1998

SQ · Multiple sites · 1–3×/day

SS-31

Cardiolipin-binding · Mitochondrial protective

40 mgDaily doseSzeto 2014

Phase 3Evidence levelSzilagyi 2009 Szeto 2014

~3 hrHalf-life

SQ · Abdomen · Once daily

01Mechanism of Action

Parameter

Ipamorelin

SS-31

Primary target

Ghrelin receptor (GHS-R1a) on anterior pituitaryRaun 1998

Cardiolipin in inner mitochondrial membraneSzeto 2014

Pathway

GHS-R1a binding → Gαq/11 → ↑intracellular Ca²⁺ → GH vesicle exocytosisRaun 1998 Bowers 1991

Cardiolipin binding → cristae stabilisation → ETC integrity → reduced ROS + preserved ATP synthesisSzeto 2014 Szilagyi 2009

Downstream effect

GH pulse amplification, IGF-1 elevation, recovery and lipolytic effectsBowers 2002

Mitochondrial bioenergetic preservation; cardio-, neuro-, and reno-protective effects in animal + clinical studiesSzeto 2014

Feedback intact?

Yes — pulsatile pattern preserved; somatostatin feedback activeBowers 2002

—

Origin

Pentapeptide H-Aib-His-D-2-Nal-D-Phe-Lys-NH₂; rationally designed for ghrelin-receptor selectivityRaun 1998

Synthetic tetrapeptide D-Arg-Dmt-Lys-Phe-NH₂; cell-permeable, mitochondrial-selectiveSzeto 2014

Antibody development

Not reported in short-term studies

—

02Dosage Protocols

Parameter

Ipamorelin

SS-31

Standard dose

200–300 mcg per injectionRaun 1998

Anecdotal community range; clinical doses 1–3 mg IV in trials.

40 mg / day SQ (clinical trials)Szeto 2014

Anecdotal community range 5-10 mg/day. Phase 3 trials use 40 mg.

Frequency

1–3× per day

Once daily pre-sleep is most common; twice or thrice for advanced users.

Once daily

Lower / starter dose

100 mcg per dose

5 mg / day (anecdotal)

Evidence basis

Phase 1 + clinical practiceRaun 1998 Sigalos 2018

Multiple Phase 3 trials (Barth, AMD, ischemia-reperfusion)Szeto 2014 Szilagyi 2009

Duration

8–12 weeks on / 4 weeks off (anecdotal)

GHS-R desensitisation reported with continuous dosing.

Indefinite for mitochondrial disease; cycled for healthspan use

Reconstitution

Bacteriostatic water; typical 2 mL per 5 mg vial

Bacteriostatic water

Timing

Pre-sleep + fasted preferred; 30 min away from food

Morning fasted preferred; pre-workout for exercise-induced mitochondrial stress

Half-life

~2 hoursRaun 1998

Longer than GHRP-6 (15 min); shorter than CJC-1295-DAC (~8 days).

~3 h plasma; tissue uptake longer

04Side Effects & Safety

Parameter

Ipamorelin

SS-31

Cortisol elevation

Negligible vs other GHRPsRaun 1998

—

Prolactin elevation

NegligibleRaun 1998

—

Hunger

Mild appetite increase via ghrelin-receptor crosstalk

—

Injection site reaction

Mild irritation possible

Erythema, mild pruritus

GH excess (overdose)

Joint pain, edema, insulin resistance

—

IGF-1 elevation

Dose-dependent; monitor with chronic high-dose use

—

Cancer risk

Theoretical via GH/IGF-1 axis; contraindicated in active malignancy

—

Pregnancy / OB

Avoid

Avoid — insufficient data

GI symptoms

—

Nausea (uncommon)

Headache

—

Reported in some Phase 3 trials

Cardiovascular

—

Cardio-protective in studies; no signal of harm

Long-term safety

—

Phase 3 data over 24+ months; no major safety signalsSzeto 2014

Absolute Contraindications

Ipamorelin

·Active malignancy or cancer history
·Pregnancy / breastfeeding
·Disrupted hypothalamic-pituitary axis

SS-31

·Pregnancy / breastfeeding
·Hypersensitivity to peptide

Relative Contraindications

Ipamorelin

·Untreated diabetes
·Severe insulin resistance
·Concurrent corticosteroid use (theoretical desensitisation)

SS-31

·None established

05Administration Protocol

Parameter

Ipamorelin

SS-31

1. Reconstitution

Add 2 mL bacteriostatic water to 5 mg vial → 2.5 mg/mL. Roll gently. Solution should be clear.

Add bacteriostatic water per label. Light-protected handling.

2. Injection site

Subcutaneous, abdomen or thigh. Rotate sites. Pinch fat for shallow SQ delivery.

SQ — abdomen or thigh. Rotate sites.

3. Timing

Pre-sleep optimal — aligns with natural GH pulse. Some protocols add a morning fasted dose.

Morning fasted; pre-workout for exercise-augmented mitochondrial stress.

4. Storage

Lyophilised: room temp, protected from light. Reconstituted: refrigerate 2–8 °C, use within 30 days.

Lyophilised: refrigerate, light-protected. Reconstituted: refrigerate ≤30 days.

5. Needle

29–31G, 4–8 mm insulin syringe.

06Stack Synergy

Ipamorelin

+ Tesamorelin

Strong

View Tesamorelin →

Ipamorelin (GHRP) + tesamorelin (GHRH analogue) is the textbook dual-axis GH stack. They activate two distinct pituitary receptors — the ghrelin receptor and the GHRH receptor — producing a synergistic GH pulse larger than either alone. Ipamorelin's selectivity (no cortisol/prolactin spike) makes it the ideal GHRP partner for long-term protocols.

Ipamorelin: 200–300 mcg SQ · pre-sleep
Tesamorelin: 2 mg SQ · same injection · pre-sleep
Primary benefit: Maximal GH pulsatility, fat loss, recovery, sleep depth

Raun 1998 Bowers 2002

+ CJC-1295 (no DAC)

Strong

View CJC-1295 (no DAC) →

CJC-1295 (no DAC) is a short-acting GHRH analogue. Combined with ipamorelin (GHRP), the pulse is amplified across both receptor systems with timing similar to native physiology. Without the DAC modification, the stack maintains sharp peaks rather than the sustained elevation seen with CJC-1295-DAC + ipamorelin.

Ipamorelin: 200–300 mcg SQ · pre-sleep
CJC-1295 (no DAC): 100 mcg SQ · same injection
Primary benefit: Pulsatile GH stimulation matching physiological pattern

Teichman 2006 Ionescu 2006

SS-31

+ MOTS-c

Moderate

View MOTS-c →

SS-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