Side-by-side · Research reference

SermorelinvsSS-31

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

APhase 3Reviewed14/43 cited

BPhase 3Reviewed9/43 cited

Sermorelin

GHRH 1-29 fragment · Short-acting

100–500 mcgPer doseMolteno 2013

Phase 3Evidence levelWalker 1994 Molteno 2013

~12 minHalf-lifeMolteno 2013

SQ · Pre-sleep · 1×/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

Sermorelin

SS-31

Primary target

Pituitary GHRH receptorWalker 1994

Cardiolipin in inner mitochondrial membraneSzeto 2014

Pathway

GHRH-R → Gαs → cAMP → PKA → GH vesicle exocytosisWalker 1994

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

Downstream effect

Pulsatile GH release; subsequent IGF-1 elevationMolteno 2013

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

Feedback intact?

Yes — short pulse preserves feedback

—

Origin

Unmodified active 29-AA fragment of human GHRH (1-44)Walker 1994

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

Antibody development

—

02Dosage Protocols

Parameter

Sermorelin

SS-31

Standard dose

100–500 mcg per injectionMolteno 2013

40 mg / day SQ (clinical trials)Szeto 2014

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

Frequency

Once daily, pre-sleep

Once daily

Lower / starter dose

100 mcg per dose

5 mg / day (anecdotal)

Evidence basis

Phase 3 (Geref pediatric); clinical practiceWalker 1994 Molteno 2013

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

Duration

8–12 weeks per cycle

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

~12 min (plasma)Molteno 2013

Shorter than tesamorelin (~26 min) — simpler GHRH analogue.

~3 h plasma; tissue uptake longer

04Side Effects & Safety

Parameter

Sermorelin

SS-31

Injection site reaction

Mild erythema, transient pain

Erythema, mild pruritus

Flushing / headache

Common transient effect

—

IGF-1 elevation

Modest at standard doses

—

Cancer risk

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

—

Pregnancy / OB

Avoid

Avoid — insufficient data

Glucose handling

Generally neutral

—

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

Sermorelin

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

SS-31

·Pregnancy / breastfeeding
·Hypersensitivity to peptide

Relative Contraindications

Sermorelin

·Untreated diabetes

SS-31

·None established

05Administration Protocol

Parameter

Sermorelin

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.

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

Sermorelin

+ Ipamorelin

Strong

View Ipamorelin →

Sermorelin (GHRH analogue) and ipamorelin (selective GHRP) form the prototypical GHRH+GHRP dual-axis stack at the lowest cost. Both peak within 30 min and produce a sharp physiological GH pulse without cortisol/prolactin elevation.

Sermorelin: 200–300 mcg SQ · pre-sleep
Ipamorelin: 200–300 mcg SQ · same injection
Primary benefit: Pulsatile GH stimulation, recovery, body composition

Raun 1998 Walker 1994

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