SS-31 Dosing: 500mcg Protocol & Timing (2026)
SS-31 (Elamipretide) dosing guide with 500mcg protocols, 5-on-2-off cycling, clinical trial context, and timing.

SS-31 (Elamipretide) is a synthetic mitochondria-targeted tetrapeptide that stabilizes cardiolipin in the inner mitochondrial membrane, restoring electron transport chain efficiency and ATP production. It's one of the few mitochondrial peptides with human clinical trial data, providing more robust dosing information than most research peptides.
SS-31 is not FDA-approved. Everything below reflects published clinical trial and community protocols. This is not medical advice.
Quick Reference: Community Dosing
If you're here for the practical protocol, here it is:
| Parameter | Standard Protocol |
|---|---|
| Dose | 500 mcg daily |
| Route | Subcutaneous injection (abdomen or thigh) |
| Frequency | 5 days on, 2 days off |
| Cycle | 8 weeks on, 8 weeks off |
| Vial size | 5 mg |
| Reconstitution | 1 mL bacteriostatic water per 5 mg vial |
| Storage | Refrigerate, use within 28 days |
Most people follow: 500 mcg daily (10 units on insulin syringe) for 5 consecutive days, then 2 days off. Continue this pattern for 8 weeks, then take 8 weeks off before repeating.
For the full SS-31 peptide profile, vendor pricing, and stack protocols, see our SS-31 peptide page.
Loading vs Maintenance
Unlike some peptides, SS-31 community protocols don't typically use a loading phase. The standard approach is:
Consistent Protocol: 500 mcg daily with 5 on / 2 off pattern throughout the entire 8-week cycle. SS-31's rapid mitochondrial uptake (>1000-fold concentration within minutes) means loading isn't necessary.
Cycle Pattern: 8 weeks on, 8 weeks off. This cycling approach prevents potential receptor desensitization while allowing assessment of sustained effects.
Timing Considerations
- Morning injection: Most common, may support daytime energy levels
- Pre-workout: Some users prefer dosing 30-60 minutes before training
- Consistent timing: Same time daily for optimal mitochondrial rhythm support
Routes of Administration
Subcutaneous Injection (Most Common)
The standard route for community protocols. Inject into abdomen, thigh, or anywhere with subcutaneous fat.
- Absorption: Provides sustained release from injection site
- Convenience: Easy for daily self-administration
- Volume: Typically 0.1 mL with insulin syringe (29-31 gauge)
Intravenous
Used only in clinical trials for:
- Phase I safety studies (single doses)
- Acute clinical models during medical procedures
- Research settings with medical supervision
IV provides rapid peak plasma levels but shorter tissue exposure than SC.
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Where These Numbers Come From: Clinical Context
The community doses above are dramatically different from clinical trial doses โ here's why:
Clinical Trial Doses (Medical Applications)
SS-31 clinical trials used much higher doses for severe medical conditions:
TAZPOWER Trial (Barth Syndrome): 40 mg SC daily for 12 weeks in patients with genetic cardiolipin deficiency โ a life-threatening condition causing heart failure (Thompson et al., 2021).
PROGRESS-HF Trial (Heart Failure): 4 mg SC daily for 4 weeks in patients with heart failure and reduced ejection fraction.
Phase I Safety: IV doses up to 250 mcg/kg (~17.5mg for 70kg adult) in single-dose safety testing (Szeto, 2014).
Preclinical Research Doses
Animal studies use 0.1โ3 mg/kg doses:
- Mice: 1โ3 mg/kg SC or IP for aging and exercise studies
- Rats: 0.1โ1 mg/kg for ischemia-reperfusion protection
- Human equivalent: ~17mg single dose from mouse studies
Why Community Doses Are Much Lower
Clinical trials used 4-40mg daily for severe genetic/cardiac conditions (Barth syndrome, heart failure) where massive mitochondrial dysfunction required aggressive intervention. Community protocols use 500mcg for several reasons:
- Different applications: General longevity/mitochondrial support vs. treating serious disease
- Saturable binding: SS-31 binds cardiolipin with high affinity โ there's a finite amount to stabilize
- Conservative extrapolation: Community doses are extrapolated conservatively from preclinical data
- Cycling approach: Lower daily dose with cycling may provide sustained benefits without desensitization
- Safety margin: 500mcg provides substantial mitochondrial uptake (>1000-fold concentration) with minimal risk
Mechanism of Action
SS-31 selectively concentrates in mitochondria (>1000-fold within minutes) where it binds cardiolipin, stabilizing electron transport chain complexes to improve ATP production while reducing ROS at the source. It's one of the fastest-acting peptides documented, improving mitochondrial ADP sensitivity within 1 hour. For the complete mechanism breakdown including cardiolipin binding, clinical trial results, and research context, see our SS-31 (Elamipretide) Research Guide.
Side Effects & Safety
SS-31 has excellent safety data from both clinical trials and community use.
What Clinical Trials Show
- 40 mg daily well-tolerated for 12+ weeks (TAZPOWER trial)
- 4 mg daily well-tolerated for 4 weeks (PROGRESS-HF)
- Phase I: No dose-limiting toxicity up to 0.25 mg/kg IV
- No significant adverse events in any trial
What Community Reports Show
At 500 mcg daily, side effects are rare:
- Occasional mild injection site irritation
- Rare reports of initial energy fluctuations (first few days)
- Generally very well-tolerated
Theoretical Considerations
SS-31's rapid mitochondrial effects are generally considered beneficial, but some theoretical considerations include:
- Potential for disrupting cellular energy balance if mitochondria are severely damaged
- Unknown long-term effects of chronic cardiolipin stabilization (though no negative signals in trials)
Stacking SS-31
SS-31 is often combined with other longevity and metabolic peptides.
SS-31 + MOTS-c
MOTS-c works through AMPK activation while SS-31 directly stabilizes mitochondrial structure. Complementary mechanisms:
| Peptide | Mechanism | Community Protocol |
|---|---|---|
| SS-31 | Direct cardiolipin binding, immediate ETC stabilization | 500 mcg daily, 5 on 2 off |
| MOTS-c | AMPK activation, metabolic signaling | 2-5 mg 2-3x/week |
SS-31 + NAD+ Precursors
SS-31 optimizes existing mitochondrial function while NAD+ precursors (NMN, NR) support mitochondrial biogenesis and repair pathways.
SS-31 + Epitalon
Epitalon targets telomerase activation while SS-31 handles mitochondrial optimization โ covering two key aspects of cellular aging.
For the full head-to-head comparison with MOTS-c, see our SS-31 vs MOTS-c comparison.
Frequently Asked Questions
What is the standard SS-31 dose for mitochondrial support?
The most common community protocol is 500 mcg daily, 5 days on / 2 days off, 8 weeks on / 8 weeks off. This is much lower than clinical trial doses (4-40mg daily) used for severe genetic/cardiac conditions.
Why is community SS-31 dosing so much lower than clinical trials?
Clinical trials used 4-40mg daily for severe conditions like Barth syndrome and heart failure. Community protocols use 500mcg extrapolated conservatively from preclinical data for general longevity/mitochondrial support, not treating disease.
How do I reconstitute SS-31?
Add 1 mL bacteriostatic water to a 5 mg vial for 5,000 mcg/mL concentration. 500 mcg = 10 units on an insulin syringe. Store refrigerated, use within 28 days.
Can SS-31 be taken orally?
No. SS-31 is a tetrapeptide that would be destroyed by digestive enzymes. All protocols use subcutaneous or intravenous injection.
How fast does SS-31 work?
Preclinically, SS-31 improves mitochondrial function within 1 hour. Community users typically run 8-week cycles to assess effects on energy, exercise capacity, and recovery.
Should I cycle SS-31 or use it continuously?
Most community protocols cycle: 8 weeks on, 8 weeks off. Within each cycle, 5 days on / 2 days off is common to prevent potential receptor desensitization.
What's the difference between SS-31 and MOTS-c dosing?
SS-31 uses much lower doses (500mcg daily) with rapid cardiolipin binding. MOTS-c needs higher doses (5-15mg/kg in animals) for AMPK signaling. SS-31 works in minutes while MOTS-c takes hours to days.
How long should I run SS-31?
Most community protocols run 8-week cycles with 8 weeks off. Some extend to 12 weeks for specific applications, but cycling is preferred over continuous use.
Related Guides
- SS-31 Peptide Page โ Vendor pricing, stack protocols, and full peptide profile
- SS-31 (Elamipretide): Research Guide โ Mechanism, cardiolipin binding, and research benefits
- SS-31 vs MOTS-c โ Two mitochondrial peptides, different mechanisms
- MOTS-c Peptide Page โ Endogenous mitochondrial peptide for metabolic health
- Epitalon Peptide Page โ Telomerase activator for cellular longevity
- Peptide Stacking Guide โ How to combine peptides effectively
References
| Citation | Topic | PMID |
|---|---|---|
| Zhao et al., J Biol Chem (2004) | SS-31 discovery, mitochondrial targeting | 15178689 |
| Birk et al., J Am Soc Nephrol (2013) | Cardiolipin binding mechanism | 23813215 |
| Szeto, Br J Pharmacol (2014) | Comprehensive SS-31 review, Phase I data | 24117165 |
| Siegel et al., Aging Cell (2013) | Rapid mitochondrial improvement in aged mice | 23692570 |
| Siegel et al., GeroScience (2023) | ADP sensitivity in aging human muscle | 37462785 |
| Thompson et al., Genet Med (2021) | TAZPOWER trial (Barth syndrome) | 33077895 |
| Campbell et al., Free Radic Biol Med (2019) | Age-related redox stress reversal | 30597195 |
| Szeto et al., J Am Soc Nephrol (2011) | Kidney ischemia-reperfusion protection | 21546574 |
| Dai et al., J Am Coll Cardiol (2011) | Hypertensive cardiomyopathy | 21620606 |
| Eirin et al., J Am Heart Assoc (2016) | Renovascular hypertension (swine) | 27247333 |
For educational and research purposes only โ no clinical use is approved. This is not medical advice. SS-31 is not FDA-approved for any indication.