Side-by-side · Research reference

SS-31vsTesofensine

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

APhase 3Reviewed9/43 cited

BPhase 3Draft10/40 cited

SS-31

Cardiolipin-binding · Mitochondrial protective

40 mgDaily doseSzeto 2014

Phase 3Evidence levelSzilagyi 2009 Szeto 2014

~3 hrHalf-life

SQ · Abdomen · Once daily

Tesofensine

SNDRI · Phase 3 obesity candidate

0.25–0.5 mgDaily doseAstrup 2008

9.2 kgWeight ↓ (24 wk)Astrup 2008

Phase 3Evidence levelAstrup 2008

Oral · Once daily morning

01Mechanism of Action

Parameter

SS-31

Tesofensine

Primary target

Cardiolipin in inner mitochondrial membraneSzeto 2014

Serotonin / norepinephrine / dopamine transporters (SERT / NET / DAT)Astrup 2008

Pathway

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

Triple monoamine reuptake inhibition → ↑synaptic 5-HT, NE, DA → appetite suppression + thermogenesisAstrup 2008

Downstream effect

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

Strong appetite suppression, mild thermogenic effect, weight lossAstrup 2008

Feedback intact?

—

Origin

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

Small molecule developed by NeuroSearch (Denmark) for CNS indications, repurposed for obesityAstrup 2008

Antibody development

—

02Dosage Protocols

Parameter

SS-31

Tesofensine

Standard dose

40 mg / day SQ (clinical trials)Szeto 2014

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

0.25–0.5 mg / dayAstrup 2008

Frequency

Once daily

Once daily, morning

Lower / starter dose

5 mg / day (anecdotal)

0.125 mg / day

Evidence basis

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

Phase 2b + ongoing Phase 3Astrup 2008

Duration

Indefinite for mitochondrial disease; cycled for healthspan use

24 weeks per studied cycle

Reconstitution

Bacteriostatic water

—

Timing

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

Morning to avoid sleep disruption

Half-life

~3 h plasma; tissue uptake longer

~9 days (very long)

Form

—

Oral capsule

04Side Effects & Safety

Parameter

SS-31

Tesofensine

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

Contraindicated

Heart rate / BP

—

Dose-dependent ↑ HR + BPAstrup 2008

Insomnia

—

Dose-related; mitigate with morning timing

Dry mouth

—

Common

Nausea

—

Common

Mood changes

—

Anxiety / agitation possible

Cardiovascular events

—

Phase 3 trial monitoring; not yet FDA-cleared

Absolute Contraindications

SS-31

·Pregnancy / breastfeeding
·Hypersensitivity to peptide

Tesofensine

·Pregnancy / breastfeeding
·Severe cardiovascular disease
·Concurrent MAOI use

Relative Contraindications

SS-31

·None established

Tesofensine

·Hypertension
·Anxiety disorder
·Insomnia

05Administration Protocol

Parameter

SS-31

Tesofensine

1. Reconstitution

Add bacteriostatic water per label. Light-protected handling.

Oral capsule (investigational; not commercial).

2. Injection site

SQ — abdomen or thigh. Rotate sites.

Swallow whole with water, morning only.

3. Timing

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

Morning to mitigate insomnia. Do not dose evening.

4. Storage

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

Room temp ≤25 °C, dry place.

5. Needle

29–31G, 4–8 mm insulin syringe.

Monitor BP + HR + mood. Avoid stimulants + MAOIs.

06Stack Synergy

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

Tesofensine

— no documented stacks