Emerging evidence · Grade B
SS-31
Elamipretide (SS-31)
Score
64 / 100
Class
Mito-targeted tetrapeptide
Target
Cardiolipin
Status
Investigational (trials mostly negative)
TL;DR
01
A mitochondria-targeted tetrapeptide (elamipretide) that concentrates in the inner mitochondrial membrane and stabilizes cardiolipin, aiming to restore energy production and reduce oxidative stress.
02
It is the most clinically tested peptide in this longevity group — with real phase 2/3 trials in mitochondrial diseases, heart failure, and eye disease.
03
The sobering part: its pivotal controlled trials largely missed their primary endpoints (Barth syndrome's controlled phase, primary mitochondrial myopathy, and dry AMD).
04
The encouraging signals tend to come from open-label extensions and secondary measures, which are weaker forms of evidence.
05
It is not approved anywhere, and its consumer supply is research-grade and unregulated.
Human trials
Multiple (ph 2/3)
most-tested in this group
Primary endpoints
Mostly missed
Barth controlled, myopathy, AMD
Positive signals
Open-label/secondary
weaker evidence
Mechanism
Cardiolipin stabilization
improves mito energy (preclinical)
Approval
None
research-grade supply
Part 01 · How it works
Mechanism.
SS-31 (elamipretide) is a small peptide engineered to home in on mitochondria — the cell's power plants — where it binds a membrane lipid called cardiolipin and helps keep the energy-production machinery intact. In cells and aged animals, that restores ATP output and cuts oxidative stress, which is a compelling rationale for fatigue, mitochondrial disease, and aging. But when it's been tested in well-controlled human trials, it has mostly failed to beat placebo on the main outcomes. The mechanism is real; the clinical payoff has been elusive.
A repair crew that reliably targets the cell's power plants and tidies them up in the lab — but in the actual controlled human trials, the lights didn't measurably come on brighter than placebo.
Mitochondrial targeting
Concentrates ~1,000-fold in the inner mitochondrial membrane.
Cardiolipin binding
Interacts with cardiolipin to stabilize cristae structure and electron-transport efficiency.
Redox effect
Reduces mitochondrial ROS and restores ATP production in aged/diseased models.
Evidence stage
Extensive human trials — but pivotal controlled endpoints largely not met.
Part 02 · Dosing & administration
How it's taken.
Clinical · trial-validatedValues below describe how SS-31 has been administered in human clinical trials and/or approved labeling. Provided for educational purposes only — this is not medical advice and not instructions for self-administration. Consult your healthcare provider before making any health decision.
Trial
40 mg/day
Subcutaneous dose used in trials; not an approved consumer regimen.
·
Doses below are from clinical trials, not instructions.
·
Given subcutaneously in the trial programs.
·
No approved regimen; consumer supply is research-grade and unregulated.
Need help with reconstitution?
Use the free peptide calculator for dilution, unit conversion, and injection volume.
Part 03 · Safety
Side effects, rare serious events, who shouldn't.
Common
Injection-site reactions
The most frequently reported effect in trials.
Common
Headache
Transient.
Reported
Serious · rare
Long-term safety
Trials were mostly short/medium term; long-term human data limited.
Limited data
Product-quality risk
Research-grade supply may not match labeled purity/dose.
Source-dependent
Absolute · do not use
×
Pregnancy or breastfeeding
×
Children under 18
×
Known hypersensitivity to elamipretide or any component
×
Severe renal impairment (clearance may be affected)
Relative · discuss first
!
Reliance on it as a proven therapy — controlled trials largely negative
!
Pregnancy or breastfeeding — insufficient data
!
Anyone expecting a demonstrated clinical benefit — the endpoints were mostly missed
Interactions
Cardiolipin-targeting drugs
Elamipretide targets mitochondrial cardiolipin; other drugs affecting mitochondrial membrane composition may interact
Moderate
Statins
Both affect mitochondrial function; theoretical additive effects on muscle mitochondria (myopathy risk)
Moderate
Coenzyme Q10 supplements
Both support mitochondrial electron transport chain; additive effects likely benign but clinical significance not established
Minor
Labs to monitor
CMP (Comprehensive Metabolic Panel)
Baseline and every 3 months
Liver and kidney function
CBC with Differential
Baseline and every 3 months
General safety monitoring
BNP or NT-proBNP
Baseline and at end of treatment
Cardiac function marker (studied in heart failure)
Creatinine & eGFR
Baseline and every 3 months
Renal function (studied in kidney disease)
Part 04 · Evidence
How strong is the evidence?
64
Grade B
Grade B, Emerging — an unusual profile where the caveat is not lack of testing but disappointing results. Strong mechanism and the most human data in this group, yet pivotal controlled trials mostly missed their primary endpoints, and it remains unapproved.
Mechanistic plausibility
Well-characterized cardiolipin-stabilization mechanism with strong preclinical support.
82
Human evidence
Multiple phase 2/3 trials — genuinely the most-tested here.
68
Outcome benefit
Pivotal controlled endpoints largely missed; positive signals mostly open-label/secondary.
45
Safety & tolerability
Generally tolerated in trials (injection-site reactions common); long-term data limited.
70
Independence
Sponsor-run program (Stealth BioTherapeutics) plus independent academic mechanistic work.
62
Part 05 · Research log
Every study we cite.
We list each study with its methodology, funding source, and our quality grade. Flagged studies aren't dismissed — they're tagged so you can weigh them.
01
2020
Genetics in Medicine Industry funded
Elamipretide in Barth syndrome — phase 2/3 crossover + open-label extension
In the controlled crossover, NEITHER primary endpoint (6-minute walk, symptom scale) was met; the uncontrolled open-label extension showed improvements at 36 weeks.
Randomized, double-blind, placebo-controlled crossover, then open-label extension · n = 12 · Small; the positive results come from the uncontrolled extension, weaker than the negative controlled phase.
PMID 33077895 ↗
Moderate
02
2018
Free Radic Biol Med Flagged
SS-31 reverses age-related redox stress and improves exercise tolerance in aged mice
8 weeks of SS-31 restored mitochondrial ATP capacity and redox balance and increased treadmill endurance in aged mice — mechanistic support for the aging rationale.
Aged-mouse study · Animal mechanism; supportive but not clinical evidence.
PMID 30597195 ↗
Moderate (preclinical)
Evidence against
What didn't work, and where the evidence is thin.
Every publication is incentivized to tell you a peptide works. We catalogue the null results, failed trials, and mechanism limits we found in the same literature — so you can weigh them against the upside, with your provider.
01
Pivotal controlled trials largely missed their primary endpoints
Failed trial Genetics in Medicine · 2020
In the controlled phase of the Barth syndrome trial, neither primary endpoint was met; the drug's larger programs in primary mitochondrial myopathy and dry age-related macular degeneration also missed their primary endpoints. Positive results tend to come from open-label extensions and secondary measures.
What this means: Despite an elegant mechanism and years of trials, SS-31 has not delivered a clear controlled-trial win — a strong caution against assuming it 'works' for fatigue or aging.
PMID 33077895 ↗
02
Well-tested, but still unapproved
Mechanism limit regulatory status · 2020
After extensive clinical development, elamipretide is not approved by any major regulator for any indication.
What this means: This isn't an untested novelty that just needs trials — it has had them, and the results haven't supported approval. That is meaningful negative information.
PMID 33077895 ↗
Part 06 · Cost & access
Where it's available, at what price.
United States
Not approved
Not FDA-approved; investigational. Consumer supply is research-grade.
Grey-market; unregulated
European Union
Not approved
Not approved.
N/A
United Kingdom
Not approved
Not approved.
N/A
Canada
Not approved
Not approved.
N/A
The Peptide Column takes no affiliate commission from any source. SS-31 (elamipretide) has been extensively tested but is not approved anywhere, and its pivotal controlled trials largely missed their endpoints; consumer supply is research-grade and unregulated. We link only to clinician-directed care, never to sellers.
Part 07 · Your appointment
Questions to bring.
01
Has SS-31/Elamipretide received FDA approval, and what is its current clinical trial status?
02
Am I a candidate for SS-31 based on any mitochondrial dysfunction or cardiac conditions?
03
What monitoring would be required if I were to use SS-31 off-label?
04
Are there any known drug interactions with cardiac medications or antioxidant therapies?
References
Every citation, numbered.
Citation list. For our editorial read of each study — including bias flags and quality grades — see the Research log above.
- 01. Elamipretide in Barth syndrome — phase 2/3 crossover + open-label extension · Genetics in Medicine, 2020 · PMID 33077895 ↗
- 02. SS-31 reverses age-related redox stress and improves exercise tolerance in aged mice · Free Radic Biol Med, 2018 · PMID 30597195 ↗
- 03. Stealth BioTherapeutics. Elamipretide clinical program (Barth, mitochondrial myopathy, AMD)