Side-by-side · Research reference

HexarelinvsSS-31

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

APhase 1Reviewed19/45 cited

BPhase 3Reviewed9/43 cited

Hexarelin

Hexapeptide GHRP · Cardio-tropic

100–200 mcgPer doseSmith 1996

Phase 1Evidence levelGhigo 1997

~70 minHalf-lifeSemenistaya 2010

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

Hexarelin

SS-31

Primary target

Ghrelin receptor (GHS-R1a) + cardiac CD36Smith 1996 Ghigo 1997

Cardiolipin in inner mitochondrial membraneSzeto 2014

Pathway

GHS-R1a → Gαq → Ca²⁺ → GH release. CD36 engagement → direct cardio-tropic actionGhigo 1997

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

Downstream effect

Strong GH pulse + IGF-1 elevation; cardio-protective effects in animal MI modelsGhigo 1997

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

Feedback intact?

Yes initially; tachyphylaxis with chronic useGhigo 1997

—

Origin

Synthetic hexapeptide His-D-2-Methyl-Trp-Ala-Trp-D-Phe-Lys-NH₂Smith 1996

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

Antibody development

—

02Dosage Protocols

Parameter

Hexarelin

SS-31

Standard dose

100–200 mcg per injectionSmith 1996

40 mg / day SQ (clinical trials)Szeto 2014

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

Frequency

1–2× per day max (tachyphylaxis with chronic 3× daily)

Once daily

Lower / starter dose

50 mcg per dose

5 mg / day (anecdotal)

Evidence basis

Phase 1 / Phase 2 trialsSmith 1996 Ghigo 1997

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

Duration

4–8 weeks on / 4–8 weeks off (tachyphylaxis mitigation)

Indefinite for mitochondrial disease; cycled for healthspan use

Reconstitution

Bacteriostatic water

Timing

Pre-sleep + fasted preferred

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

Half-life

~70 minSemenistaya 2010

~3 h plasma; tissue uptake longer

04Side Effects & Safety

Parameter

Hexarelin

SS-31

Cortisol elevation

Modest at high dosesGhigo 1997

—

Prolactin elevation

Modest at high dosesGhigo 1997

—

Hunger

Strong appetite increase via ghrelin agonism

—

Tachyphylaxis

Receptor desensitisation with chronic dosingGhigo 1997

—

Cardiac effects

Direct cardio-tropic; potential benefit in MI but unstudied in humansGhigo 1997

—

IGF-1 elevation

Strong; monitor with chronic high-dose use

—

Cancer risk

Contraindicated in active malignancy (GH/IGF-1 axis)

—

Pregnancy / OB

Avoid

Avoid — insufficient data

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

Long-term safety

—

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

Absolute Contraindications

Hexarelin

·Active malignancy
·Pregnancy / breastfeeding
·Disrupted hypothalamic-pituitary axis

SS-31

·Pregnancy / breastfeeding
·Hypersensitivity to peptide

Relative Contraindications

Hexarelin

·Untreated diabetes
·Severe hyperprolactinemia

SS-31

·None established

05Administration Protocol

Parameter

Hexarelin

SS-31

1. Reconstitution

Add 2 mL bacteriostatic water to 5 mg vial → 2.5 mg/mL = 250 mcg per 0.1 mL.

Add bacteriostatic water per label. Light-protected handling.

2. Injection site

SQ — abdomen or thigh. Rotate sites.

3. Timing

Pre-sleep + fasted preferred. Cycle on/off to avoid tachyphylaxis.

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

4. Storage

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

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

5. Needle

29–31G, 4–8 mm insulin syringe.

06Stack Synergy

Hexarelin

+ CJC-1295 (no DAC)

Strong

View CJC-1295 (no DAC) →

Hexarelin (GHRP) + CJC-1295-no-DAC (GHRH analogue) is the higher-amplitude variant of the standard GHRH+GHRP stack. Hexarelin produces a stronger pulse than ipamorelin but with cortisol + prolactin signal — choose this stack for maximum GH amplitude when side-effect tolerance is acceptable. Cycle aggressively.

Hexarelin: 100 mcg SQ · pre-sleep
CJC-1295 (no DAC): 100 mcg SQ · same injection
Primary benefit: Maximum GH pulse amplitude (with side-effect signal)

Smith 1996 Teichman 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