Peptide Protocol IQ

Mitochondrial Research

Mitochondrial-derived peptides, cardiolipin interaction, oxidative phosphorylation, and exercise capacity.

Often described colloquially as “Energy and mitochondria”. We use research terminology because the colloquial phrasing implies an outcome the evidence often does not support.

2 graded claims1 with human evidence2 compounds

Compounds

Examined in this research area

DPreclinical

MOTS-c

An interesting endogenous signalling peptide with genuine mechanistic literature and essentially no human outcome evidence.

XInsufficient / conflicting

Elamipretide (SS-31)

A genuinely investigational compound with registered clinical trials and a development history that includes missed primary endpoints. A useful case study in conflicting evidence.

Evidence

Claims in this area, strongest first

Ordered by evidence level so that the state of the field is visible at a glance rather than buried.

MOTS-c

DPreclinicalLow confidenceNo human evidence

MOTS-c has been reported to influence insulin sensitivity and metabolic markers in mouse models.

What is not established

No adequate human trials. Endogenous presence does not establish that administration is safe or effective.

Supporting sources (2)
Randomised controlled trialHumanIdentifier pending verification

MOTS-c for improving insulin sensitivity in adults with prediabetes and overweight or obesity (MOTS-MET)

Hudson Biotech · Not published · 2026 · n = 120

Population
Adults with prediabetes and overweight or obesity
Endpoint
Treatment-emergent adverse events at 16 weeks; OGTT-derived insulin sensitivity at 12 weeks
Route
Subcutaneous
Quantity as reported
Not disclosed. The registry record states a fixed amount once daily for 12 weeks without naming it.
Frequency
Once daily
Duration
16 weeks

Result. Recruiting. No results.

Adverse events. Not yet reported.

Limitations. This is the first interventional human study of MOTS-c ever registered, it began in 2026, and it has no results. Until it reports, every MOTS-c quantity in circulation is extrapolated from rodent work.

NCTNCT07505745
Animal studyAnimalIdentifier pending verification

MOTS-c as a mitochondrial-derived peptide in metabolic regulation

Lee C, Zeng J, Drew BG, et al. · Cell Metabolism and related · 2015

Population
Mouse models of diet-induced obesity and insulin resistance
Endpoint
Insulin sensitivity, weight, and metabolic markers
Route
Intraperitoneal in animal models
Quantity as reported
mg/kg in animal models — not translatable
Frequency
Varies

Result. Reported improvement in insulin sensitivity and resistance to diet-induced obesity in the mouse models studied.

Adverse events. Not characterised in humans.

Limitations. Animal and mechanistic work. No adequate human outcome trials.

Search PubMed for this literature →

Last evidence review: 2026-08-23

Elamipretide (SS-31)

XInsufficient / conflictingLow confidenceHuman evidence

Elamipretide has been studied in registered trials in mitochondrial myopathy and heart failure, with inconsistent results across programmes.

What is not established

Several programmes did not meet primary endpoints. This is a conflicting-evidence record, not a positive one.

Supporting sources (1)
Randomised controlled trialHumanIdentifier pending verification

Elamipretide (SS-31) in mitochondrial disease and heart-failure programmes

Multiple · Various cardiology and neurology journals · 2021

Population
Adults with primary mitochondrial myopathy or heart failure, by programme
Endpoint
Six-minute walk distance, fatigue scales, cardiac measures by programme
Route
Subcutaneous
Quantity as reported
Reported in registered trial protocols
Frequency
Daily in most programmes
Duration
24 weeks

Result. Results across programmes have been mixed. Several endpoints did not reach statistical significance, and development history includes missed primary endpoints.

Adverse events. Injection-site reactions were common in the trials.

Limitations. This is an important example of conflicting evidence: positive early signals were not consistently confirmed in larger trials.

Search PubMed for this literature →

Last evidence review: 2026-08-23