Side-by-side · Research reference

AOD-9604vsSS-31

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

APhase 2Reviewed10/47 cited

BPhase 3Reviewed9/43 cited

AOD-9604

HGH 176-191 · β3-AR Lipolytic

250–300 mcgDaily doseHeffernan 2001

Phase 2Evidence levelHeffernan 2001 Ng 2008

~30 minHalf-life

SQ · Abdomen · Daily fasted

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

AOD-9604

SS-31

Primary target

β3-adrenergic receptor (proposed)Ng 2008

Cardiolipin in inner mitochondrial membraneSzeto 2014

Pathway

β3-AR activation → cAMP → hormone-sensitive lipase activation → triglyceride breakdown to FFA + glycerolNg 2008

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

Downstream effect

Lipolysis of adipose tissue triglycerides; FFA release for oxidation; minimal IGF-1 / insulin impactHeffernan 2001

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

Feedback intact?

No GH-axis or IGF-1 feedback

—

Origin

Synthetic modified C-terminal hexadecapeptide fragment of human GH (176-191) with N-terminal Tyr substitutionNg 2008

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

Antibody development

—

02Dosage Protocols

Parameter

AOD-9604

SS-31

Standard dose

250–300 mcg / dayHeffernan 2001

Anecdotal SQ range. Phase 2 trial dose 1 mg/day oral.

40 mg / day SQ (clinical trials)Szeto 2014

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

Frequency

Once daily, fasted

Once daily

Lower / starter dose

150 mcg / day

5 mg / day (anecdotal)

Evidence basis

Phase 2 trials + animal-strongHeffernan 2001 Ng 2008

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, 1 mL per 2 mg vial → 2 mg/mL

Bacteriostatic water

Timing

Morning fasted preferred (pre-cardio)

Aligns with circadian lipolysis.

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

Half-life

~30 min plasma

~3 h plasma; tissue uptake longer

04Side Effects & Safety

Parameter

AOD-9604

SS-31

Injection site reaction

Mild erythema

Erythema, mild pruritus

GI symptoms

Rare mild nausea

Nausea (uncommon)

Cardiovascular

Possible mild HR increase via β3-AR (theoretical β1 cross-reactivity)

Cardio-protective in studies; no signal of harm

IGF-1 elevation

None — designed to lack GH-axis activityHeffernan 2001

—

Insulin sensitivity

Neutral — no glucose impairmentHeffernan 2001

—

Cancer risk

No GH/IGF-1 axis activity → lower theoretical risk vs HGH

—

Pregnancy / OB

Avoid

Avoid — insufficient data

Headache

—

Reported in some Phase 3 trials

Long-term safety

—

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

Absolute Contraindications

AOD-9604

·Pregnancy / breastfeeding
·Severe cardiovascular disease (caution with β-receptor agonists)

SS-31

·Pregnancy / breastfeeding
·Hypersensitivity to peptide

Relative Contraindications

AOD-9604

·Concurrent β-blocker therapy (theoretical antagonism)
·Pheochromocytoma

SS-31

·None established

05Administration Protocol

Parameter

AOD-9604

SS-31

1. Reconstitution

Add 1 mL bacteriostatic water to 2 mg vial → 2 mg/mL = 200 mcg per 0.1 mL.

Add bacteriostatic water per label. Light-protected handling.

2. Injection site

SQ — abdomen preferred. Rotate sites.

SQ — abdomen or thigh. Rotate sites.

3. Timing

Morning, fasted, ideally pre-cardio for amplified fat oxidation.

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

AOD-9604

+ MOTS-c

Moderate

View MOTS-c →

AOD-9604 mobilises FFAs from adipose via β3-AR; MOTS-c upregulates AMPK / PGC-1α / FAO machinery so that mobilised FFAs are efficiently oxidised. The pathways are sequential — supply (AOD) plus demand (MOTS-c) — and produce more durable lipolytic effects than either alone in anecdotal protocols.

AOD-9604: 250–300 mcg SQ · morning fasted (daily)
MOTS-c: 5 mg SQ · 2–3× per week (pre-workout)
Primary benefit: Fat mobilisation + mitochondrial oxidation, no IGF-1 concern

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