The Peptide Reference
The Peptide Reference
References
Reference/Aromatic-cationic tetrapeptide

SS-31

Mitochondrial-Targeted Peptide · Cardiolipin Protector

Human clinical
research use only

SS-31 (Elamipretide) is an aromatic-cationic tetrapeptide that selectively binds to cardiolipin in the inner mitochondrial membrane, preventing lipid peroxidation and optimizing electron transport chain function for enhanced cellular energy production.

Directly protects mitochondriaImproves cellular energy production (ATP)Reduces oxidative damageEnhances exercise capacity
01

Overview

SS-31 (Elamipretide) is an aromatic-cationic tetrapeptide that selectively binds to cardiolipin in the inner mitochondrial membrane, preventing lipid peroxidation and optimizing electron transport chain function for enhanced cellular energy production.

Selectively binds to cardiolipin in inner mitochondrial membrane, preventing lipid peroxidation and optimizing electron transport chain function. This improves ATP production and reduces oxidative damage at the mitochondrial level.

Evidence profilederived from 6 references
A
Human clinical
Strongest design among the references on this page. Grade and effect size are separate facts and are never merged into one score.
02

Research indications

What the compound has been studied for, grouped by body system. Effect size is the reported magnitude where it was measured — not a recommendation.

Mitochondrial3
Enhanced ATP Production

Optimizes electron transport chain function for improved cellular energy.

Large
Oxidative Stress Reduction

Prevents cardiolipin peroxidation and reduces mitochondrial oxidative damage.

Large
Mitochondrial Disease Support

Significant improvements in 6-minute walk test and fatigue scores in PMM patients.

Moderate
Cardiovascular3
Cardiac Protection

Reduces cardiac injury markers and improves mitochondrial function in surgical patients.

Moderate
Heart Failure Support

Reduces ischemia-reperfusion injury and supports cardiac function.

Moderate
Exercise Tolerance

Enhanced exercise capacity and reduced fatigue.

Moderate
Anti-Aging3
Age-Related Muscle Function

Reversed age-related decline in muscle function in animal studies.

Small
Cognitive Protection

Neuroprotective effects demonstrated in Alzheimer's models.

Small
Cellular Rejuvenation

Supports overall cellular health through mitochondrial optimization.

Small
i

A large effect in a weak study and a small effect in a strong one are different things. Effect size is never evidence of use in people.

Quick factsreference only
Class
Aromatic-cationic tetrapeptide
Half-life
~2 h
Typical dose
5-10mg general support, 10-40mg clinical/performance protocols
Frequency
Once daily (morning or pre-workout for athletic use)
Cycle length
4-12 weeks for therapeutic protocols
Storage
Reconstituted: 2-8°C in amber/dark vials, use within 30 days. Light sensitive
03

Molecular data

Type
Aromatic-cationic tetrapeptide
Half-life
120 min
04

Dosing reference

Doses reported in the literature and by suppliers. These are a record of what has been used in research — reference, never instruction.

ContextRouteAmountFrequency
General mitochondrial supportSubQ5-10mgOnce daily
Athletic performanceSubQ10-20mgOnce daily pre-workout
Clinical protocolsSubQ or IV40mgOnce daily
Acute cardioprotectionIV0.25mg/kg/hrContinuous infusion
Skin anti-agingFace, neck, hands0.5-1% cream/gelTwice daily
05

Interactions

NAD+

Both support mitochondrial function through different mechanisms.

synergistic
MOTS-c

Both are mitochondrial peptides with complementary mechanisms.

synergistic
Humanin

May work together to protect cellular function.

synergistic
GHK-Cu

Different mechanisms; no conflicts.

compatible
BPC-157

BPC-157 focuses on tissue repair while SS-31 targets cellular energetics.

compatible
Thymosin Beta-4

Both cardioprotective via different pathways.

compatible
06

Quality checklist

  • Pharmaceutical grade (>98% purity required for clinical applications)
  • Clear, colorless solution after reconstitution
  • Certificate of Analysis available
  • Proper cold chain maintenance
  • !Light sensitive - protect from exposure using amber vials
  • !Solution pH should be 6.5-7.5 (physiological range)
  • ×Yellow or brown discoloration indicates degradation
  • ×Cloudy solution or visible particles
  • ×Improper storage conditions
07

What to expect

Day 1-3Subtle energy improvements, reduced fatigue
Week 1-2Better exercise endurance, faster recovery
Week 2-4Improved stamina, clearer thinking, better sleep
Week 4-8Significant exercise capacity improvements
Week 8-12Sustained energy, potential biomarker changes
08

Safety

Commonly reported4
  • Excellent safety profile in clinical trials
  • No significant side effects reported at therapeutic doses
  • Mild injection site reactions possible
  • Safe for long-term use based on current data
Stop and seek advice5
  • Severe injection site reactions
  • Allergic reaction signs (rash, breathing difficulty)
  • Unusual fatigue or weakness (paradoxical reaction)
  • Cardiovascular symptoms
  • Severe headaches or vision changes
Contraindications2
  • Known hypersensitivity to peptides
  • Pregnancy or breastfeeding (limited data)
09

FAQ

Is SS-31 light sensitive and does it really need amber vials?

Yes, SS-31 is photosensitive and requires light protection. Store reconstituted solutions in amber vials or dark containers at 2-8°C. The peptide's aromatic-cationic structure is vulnerable to photodegradation, which can compromise its mitochondrial-binding effectiveness.

How quickly does SS-31 improve exercise tolerance?

Initial improvements in energy and fatigue appear within 1-3 days, with better exercise endurance noticed by week 1-2. Peak exercise capacity improvements typically develop over 4-8 weeks as mitochondrial ATP production optimizes.

Can SS-31 be used with NAD+ boosters and will they interact?

Yes, SS-31 and NAD+ are synergistic because both target mitochondrial function through complementary mechanisms - SS-31 directly protects cardiolipin while NAD+ supports electron transport chain enzymes. Combining them may enhance energy production more than either alone.

What's the difference between clinical-grade SS-31 (40mg daily) and athletic performance doses?

Athletic protocols use 10-20mg daily, while clinical trials for mitochondrial disease used 40mg daily. The higher clinical dose targets more significant mitochondrial dysfunction; athletic users typically achieve performance benefits at lower doses with less potential for excessive metabolic stimulation.

10

References

  1. 1
    Novel Mitochondria-Targeting Peptide in Heart Failure Treatment (EMBRACE)
    Daubert, M.A., et al. · Circulation: Heart Failure · 2017

    IV infusion in heart failure patients showed significant decrease in left ventricular end-diastolic volume (-18 mL, P=0.009) and end-systolic volume (-14 mL, P=0.005) at the highest dose.

  2. 2
    Randomized Dose-Escalation Trial of Elamipretide in Adults with Primary Mitochondrial Myopathy (MMPOWER)
    Karaa, A., et al. · Neurology · 2018

    Phase I/II trial in 36 patients showed dose-dependent improvement in 6-minute walk test (64.5m vs 20.4m placebo at highest dose) after 5 days of treatment with excellent safety profile.

  3. 3
    Improving Mitochondrial Function with SS-31 Reverses Age-Related Redox Stress and Improves Exercise Tolerance in Aged Mice
    Siegel, M.P., et al. · Free Radical Biology and Medicine · 2019

    8 weeks of SS-31 (3 mg/kg/day) in aged mice reversed age-related decline in mitochondrial ATP production, restored redox homeostasis, and significantly increased treadmill endurance.

  4. 4
    TAZPOWER: Phase 2/3 Randomized Clinical Trial of Elamipretide in Barth Syndrome
    Thompson, W.R., et al. · Genetics in Medicine · 2021

    40mg daily in Barth syndrome patients. Primary endpoints not met at 12 weeks, but open-label extension showed cumulative 96.1m improvement in 6MWT at 168 weeks (P=0.003) with sustained fatigue improvements.

  5. 5
    Efficacy and Safety of Elamipretide in Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial
    Karaa, A., et al. · JAMA Neurology · 2023

    Phase 3 trial (218 patients) did not meet primary 6MWT endpoint overall, but post-hoc analysis showed improvement in patients with nuclear DNA variants. Well-tolerated with mild-to-moderate adverse events.

  6. 6
    Elamipretide: A Review of Its Structure, Mechanism of Action, and Therapeutic Potential
    Machiraju, P., et al. · International Journal of Molecular Sciences · 2025

    Comprehensive review covering PROGRESS-HF, TAZPOWER, MMPOWER-3, and ReCLAIM trials. Highlights elamipretide's unique cardiolipin-binding mechanism and broad therapeutic potential across mitochondrial diseases.

For research use only. Nothing on this page is medical advice, and no number here is a recommendation to dose.