01 — Identity

Name & Classification

SS-31 stands for Szeto-Schiller Peptide 31, named after its inventors Hazel Szeto and Peter Schiller. Its chemical name is D-Arg-2′6′-Dmt-Lys-Phe-NH₂, also known commercially as Elamipretide (MTP-131).

It is a synthetic tetrapeptide (4 amino acids) that selectively concentrates in the inner mitochondrial membrane where it binds cardiolipin — a phospholipid critical for electron transport chain function. It is classified as a mitochondria-targeted antioxidant and cardioprotective peptide.

02 — Origin

When It Was Developed

Early 2000s

Developed by Dr. Hazel Szeto at Weill Cornell Medical College. Originally designed as an opioid receptor agonist; the mitochondrial targeting was discovered serendipitously.

2004–2006

Landmark papers published showing SS-31 selectively concentrates in the inner mitochondrial membrane (IMM) and protects cardiolipin from oxidation — a completely novel mechanism.

2010s

Licensed to Stealth BioTherapeutics as Elamipretide (MTP-131). Phase 2/3 trials launched for heart failure with preserved ejection fraction (HFpEF), Barth syndrome, and primary mitochondrial myopathy.

2019–2022

Phase 3 MMPOWER-3 trial for Barth syndrome — a rare mitochondrial disease — showed functional improvement but missed primary endpoint. Research continued in cardiac, renal, and aging contexts.

2022–Present

Growing use in longevity and sports medicine. Animal studies show dramatic reversal of age-related mitochondrial dysfunction. No FDA approval; research peptide status in wellness space.

03 — Research History

Research Background

SS-31's defining mechanism is its ability to bind cardiolipin — a phospholipid unique to the inner mitochondrial membrane that is essential for organizing the electron transport chain (ETC) supercomplexes. With age and disease, cardiolipin becomes oxidized and fragmented, causing ETC inefficiency, increased ROS production, and mitochondrial collapse. SS-31 intercepts this process directly at the source.

A landmark 2021 study in Nature Aging showed that SS-31 in aged mice reversed multiple hallmarks of cardiac aging in weeks — not months — restoring mitochondrial cristae architecture, reducing oxidative stress, and improving cardiac output. This is one of the most dramatic aging reversal results seen with any single compound in animal models.

SS-31 also improves ATP production efficiency, reduces mitochondrial reactive oxygen species (ROS) without scavenging them, and preserves cytochrome c in the ETC rather than allowing its release as an apoptosis trigger.

04 — Key Benefits

Proposed Benefits

Binds and protects cardiolipin in the inner mitochondrial membrane

Restores ETC supercomplex organization and ATP synthesis efficiency

Reduces mitochondrial ROS without interfering with signaling ROS

Dramatic cardiac protection — reduces ischemia-reperfusion injury

Reverses age-related mitochondrial dysfunction in animal models

Improves exercise tolerance and physical capacity in aging

Renal protection — reduces acute kidney injury and fibrosis

Neuroprotective — improves neuronal mitochondrial function

05 — Reconstitution

10 mg Vial + 300 Units BAC Water

33.3 mcg

per unit drawn on insulin syringe

10,000

mcg total

0.3 mL

total volume

4–6 wk

shelf life (fridge)

🧊

RECONSTITUTED SHELF LIFE

21 days after mixing

Hydrophobic mitochondrial peptide. Aggregation risk with time.

            Storage: 2–8°C (fridge) · Protected from light · Do NOT freeze

            Preload syringes/cartridges to minimize vial disturbance

300 units = 0.3 mL on a U-100 insulin syringe. Store refrigerated at 36–46°F / 2–8°C after reconstitution. SS-31 is stable in solution but sensitive to repeated freeze-thaw cycles — do not freeze once reconstituted. Light-sensitive; store in original vial or amber container.

06 — Dosage

Dosage Reference

Dosage Reference (10mg vial + 3.0mL BAC = 33.3 mcg/unit)

Level	Dose	Units to Draw	Context
LOW	300 mcg	9 units	Conservative start — sensitive individuals or first cycle
STANDARD	500 mcg	15 units	Most common research dose — active mitochondrial support
HIGH	1 mg (1000 mcg)	30 units	Aggressive protocol — monitor closely

Reconstitute 10mg vial with 3.0mL BAC water = 33.3 mcg/unit. Inject subcutaneously daily. SS-31 has an extremely short plasma half-life (~30 min) but mitochondrial retention is prolonged. Injection site reactions (redness, mild pain) are the most commonly reported side effect.

07 — Monitoring

Biomarkers, Lab Tests & Ranges

SS-31 primarily acts on cardiac, mitochondrial, and renal systems. Monitor the following before starting, at 6 weeks, and at cycle end.

▸ Mitochondrial Function

Biomarker	Lab Test	Clinical Range	Optimal Range
Lactate (resting)	Serum Lactate	CLINICAL0.5–2.2 mmol/L	OPTIMAL0.5–1.0 mmol/L
CoQ10 (Ubiquinol)	Plasma CoQ10	CLINICAL0.4–1.9 µg/mL	OPTIMAL1.5–3.5 µg/mL
GDF-15 Mitochondrial stress signal	Serum GDF-15	CLINICAL<1200 pg/mL	OPTIMAL<400 pg/mL
8-OHdG Oxidative DNA damage	Urine 8-OHdG	CLINICAL<15 ng/mg creatinine	OPTIMAL<5 ng/mg creatinine

▸ Cardiac Health

Biomarker	Lab Test	Clinical Range	Optimal Range
NT-proBNP Heart stress marker	Serum NT-proBNP	CLINICAL<125 pg/mL (<75 yrs)	OPTIMAL<50 pg/mL
Troponin I / T	High-sensitivity Troponin	CLINICAL<0.04 ng/mL (standard)	OPTIMALUndetectable / baseline stable
hsCRP	High-sensitivity CRP	CLINICAL<3.0 mg/L	OPTIMAL<0.5 mg/L

▸ Renal & Metabolic Safety

Biomarker	Lab Test	Clinical Range	Optimal Range
Creatinine / eGFR	CMP	CLINICALCreat 0.7–1.3 mg/dL / eGFR >60	OPTIMALCreat 0.8–1.1 / eGFR >90
Cystatin C Sensitive kidney marker	Serum Cystatin C	CLINICAL0.5–1.0 mg/L	OPTIMAL<0.7 mg/L
AST / ALT	CMP	CLINICALAST 10–40 / ALT 7–56 U/L	OPTIMALAST <26 / ALT <26 U/L
CBC	Complete Blood Count	CLINICALStandard lab ranges	OPTIMALMid-range; WBC 4.5–6.0

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⚠ Optimal ranges reflect functional/longevity medicine targets. SS-31 is not FDA-approved. Cardiac biomarkers should be interpreted with a cardiologist if any abnormalities are present at baseline.

08 — Cycle Protocol

Cycle Length, Frequency & Timing

▸ How Long to Cycle

CLINICAL TRIAL

4–12 Weeks

Phase 2/3 trials used 4–12 week dosing windows; some chronic dosing studies extended to 6 months in mitochondrial myopathy.

PRACTITIONER CONSENSUS

8–12 Weeks

Most practitioners run 8–12 week cycles with a 4–8 week break. Some longevity protocols use continuous low-dose cycling given the strong safety profile.

SS-31 has shown no tolerance or desensitization in research literature. Its mitochondrial accumulation is rapid (within minutes) and sustained. Given its short plasma half-life, consistent daily dosing is more important than with longer-acting peptides.

▸ Frequency & Timing

Variable	Recommendation	Why
Frequency	Daily (7×/week)	SS-31 has a very short plasma half-life (~30 min). Daily dosing maintains mitochondrial cardiolipin protection continuously. Clinical trials all used daily dosing.
Fasted vs Fed	~ Either acceptable	SS-31's mechanism is not insulin-dependent. It goes directly to mitochondria regardless of metabolic state. Fasted AM is conventional but no strong preference in the data.
Morning (AM)	✓ Preferred	Morning dosing aligns with circadian mitochondrial activity peaks and ensures cardioprotection is active during the metabolically active daytime period.
Pre-exercise	✓ Strongly considered	Dosing 20–30 min before training maximizes mitochondrial protection during the oxidative stress of exercise — directly aligning with SS-31's core mechanism.
Wait to eat	~ Not critical	No evidence that food intake affects absorption or efficacy. Eat normally after injection.

PROTOCOL SUMMARY

8–12 wk

CYCLE LENGTH

Daily

FREQUENCY

AM

TIMING

Either

FED STATE

4–8 wk

BREAK