Side-by-side · Research reference

AdipotidevsSS-31

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

AAnimal-StrongHUMAN-REVIEWED15/49 cited

BPhase 3HUMAN-REVIEWED9/43 cited

Adipotide

Pro-apoptotic Vascular-Targeting Peptide · Preclinical Only

PreclinicalStatus

PHB1TargetHossen 2013

ApoptosisMechanismHossen 2013

IV · Systemic · Preclinical Protocols OnlyHossen 2013

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

Adipotide

SS-31

Primary target

Prohibitin-1 (PHB1) on adipose vasculature endotheliumHossen 2013

Cardiolipin in inner mitochondrial membraneSzeto 2014

Pathway

CKGGRAKDC domain binds PHB1 → Peptide internalisation → D(KLAKLAK)₂ mitochondrial membrane disruption

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

Downstream effect

Endothelial apoptosis → Adipose vascular collapse → Adipocyte involution → Weight loss

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

Feedback intact?

N/A — Direct apoptotic mechanism, non-hormonal

—

Origin

Synthetic bioconjugate: PHB1-targeting homing peptide + pro-apoptotic KLA sequence

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

Antibody development

—

02Dosage Protocols

Parameter

Adipotide

SS-31

Animal dose (mouse)

Low dose (not specified in abstract)Hossen 2013

Systemic injection in diet-induced obesity (DIO) models.Hossen 2013

—

Route

Intravenous (systemic injection)

—

Frequency

Not specified in available data

Once daily

Evidence basis

Preclinical animal models only

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

Human data

None — no clinical trials reported

—

Standard dose

—

40 mg / day SQ (clinical trials)Szeto 2014

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

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

Adipotide

SS-31

Primary fat target

White adipose tissue (all depots)

—

Mechanism

Vascular apoptosis → adipose blood supply collapse → adipocyte deathHossen 2013

—

Body weight reduction

Significant reduction in DIO miceHossen 2013

Absolute values not provided in abstract.

—

Leptin levels

Significant decrease

Parallel to adipose mass reduction.

—

Effect on adipocytes

Antiobesity effect on dysfunctional adipose cells (adipocytes + macrophages)Hossen 2013

—

Ectopic fat

Reduction in ectopic fat depositionHossen 2013

Marker of dysfunctional adipose tissue / metabolic syndrome.

—

Species tested

Obese rhesus monkeys, DIO mice

—

Human translation

Unknown — no clinical trials

—

04Side Effects & Safety

Parameter

Adipotide

SS-31

Safety profile

Unknown — preclinical data only

—

Vascular selectivity

Targets adipose vasculature; off-target vascular effects unknown

—

Apoptotic mechanism risk

Pro-apoptotic payload may affect unintended tissues if selectivity incomplete

—

Kidney / liver toxicity

Not reported in available data

—

Immunogenicity

Not assessed in available 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

Pregnancy / OB

—

Avoid — insufficient data

Absolute Contraindications

Adipotide

·Human use — not approved, no clinical safety data

SS-31

·Pregnancy / breastfeeding
·Hypersensitivity to peptide

Relative Contraindications

Adipotide

·Any condition requiring intact adipose-tissue vascularisation

SS-31

·None established

05Administration Protocol

Parameter

Adipotide

SS-31

1. Route

Intravenous injection (systemic) in preclinical models. No human protocols exist.

Add bacteriostatic water per label. Light-protected handling.

2. Formulation

Bioconjugate peptide. May also be encapsulated in nanoparticles (prohibitin-targeted nanoparticle formulation, KLA-PTNP, showed superior efficacy vs. free bioconjugate in mice).Hossen 2013

SQ — abdomen or thigh. Rotate sites.

3. Preclinical dosing

Low-dose systemic injection (exact dosing not specified in available abstract). Frequency and duration not detailed.Hossen 2013

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

4. Storage

Not specified — likely requires peptide-grade lyophilised storage and reconstitution.

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

5. Needle

—

29–31G, 4–8 mm insulin syringe.

06Stack Synergy

Adipotide

— no documented stacks

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