Supplement
MOTS-c
A mitochondria-encoded peptide with interesting animal metabolic data.
MOTS-c is a 16-amino-acid peptide encoded in mitochondrial DNA (discovered 2015) that activates AMPK and improves glucose metabolism in cell and mouse models, acting as an exercise-like metabolic signal. We grade MOTS-c D on evidence and D for worth-it at about $80-200 per month.
Evidence
Worth it
Typical cost: $80-200/month
What it does
MOTS-c is a 16-amino-acid peptide encoded in mitochondrial DNA (discovered 2015) that activates AMPK and improves glucose metabolism in cell and mouse models, acting as an exercise-like metabolic signal. It is a RESEARCH compound: no completed human efficacy trial of administered MOTS-c exists, and it is not approved by any health authority.
What the research says
Improves insulin resistance and obesity in mouse models
Evidence: weak. Lee et al. (Cell Metabolism, 2015) and later mouse studies show AMPK activation, increased GLUT4 and glucose uptake, and better physical performance; no human interventional data.
Circulating MOTS-c rises with exercise in humans
Evidence: moderate. Human studies are observational: endogenous MOTS-c increases after exercise, but whether injected MOTS-c reproduces exercise effects is untested.
An analog (CB4211) improved liver and glucose markers in a small Phase 1b
Evidence: weak. CohBar's modified analog, not native MOTS-c, showed ALT/AST and glucose improvements in 20 obese subjects; results were never published in a peer-reviewed journal.
Biologically fascinating but clinically unproven: the entire administered-dose evidence base is cell culture and rodents, with human data limited to observational correlations. No published human trial, no pharmacokinetic data, and no active trials of MOTS-c or its analogs.
Is it worth it?
Expensive gray-market injectable with zero human efficacy data and unknown human pharmacokinetics. For metabolic health, metformin and exercise have vastly more human evidence at a fraction of the cost.
Typical cost
$80-200/month
Common form, not a brand recommendation
Dosage contextno established dose
No human dose has been validated. Community protocols are extrapolated from animal studies and are not endorsements of any dose for any person.
Safety notes
RESEARCH COMPOUND ONLY. No human safety data exist for administered MOTS-c: optimal dose, absorption, metabolism, and long-term effects are unknown. Plausible hypoglycemia risk if combined with glucose-lowering drugs, though no interaction studies exist. Products sold online are not regulated for quality, purity, or sterility. Banned by WADA at all times.
Longevity Lab Report
MOTS-c news, graded when it happens.
New studies, dose debates, and expert shifts on mots-c, in one email a week. Free.
Changelog
Last updated 2026-10-15
- 2026-10-15|Batch 2 DRAFT entry.
- 2026-10-15|Regulatory: Feb 2026 HHS announcement moved MOTS-c toward Category 1; July 2026 FDA PCAC voted to recommend it for the 503A Bulks List (non-binding). Not FDA approval. Evidence grade unchanged. Source: https://www.ajmc.com/view/5-things-to-know-about-the-fda-s-peptide-reversal