Educational reference only. Not medical advice. Consult a healthcare provider before starting any protocol.
MOTS-c
Mitochondrial Open Reading Frame of the 12S rRNA Type-c
What it is
A 16-amino-acid mitochondrial-derived peptide encoded within the 12S rRNA gene (MT-RNR1), discovered in 2015 by Changhan Lee and Pinchas Cohen at USC. MOTS-c is studied in preclinical models as an AMPK activator via inhibition of the folate cycle and accumulation of AICAR. It has been characterized in research literature as an 'exercise mimetic' based on observations that endogenous levels increase ~11.9-fold in skeletal muscle following exercise. The only human data comes from CB4211, a discontinued MOTS-c analog that completed Phase 1a/1b (CohBar, Inc., now dissolved).
Community-reported ranges
Preclinical literature and one discontinued analog Phase 1 trial. Community dosing ranges are anecdotal with no clinical validation. Not dosing guidance.
Reported dose range
5000–15000 mcg
Estimated half-life
~1-2 hours (estimated)
Source: Inferred from exercise-induced kinetics; no formal human PK data exists
Reported cycle length
4–6 weeks on
2-4 weeks off
Route
subcutaneous
Common vial sizes
5mg, 10mg
Reported timing
AM preferred (community-reported energy-boosting effects)
Reported frequency
2-3x weekly
Frequently discussed alongside
Based on community forum discussions. Not a recommendation to combine compounds.
Published research
Discovered in 2015 (Lee et al., Cell Metabolism). Studied in preclinical models for AMPK activation via folate cycle inhibition and AICAR accumulation. Kim et al. (Cell Metabolism 2018) demonstrated stress-induced nuclear translocation where MOTS-c regulates antioxidant response elements. Reynolds et al. (Nature Communications 2021) reported ~11.9-fold increase in skeletal muscle MOTS-c following exercise. The only human-tested analog, CB4211, completed Phase 1a/1b (n=88) showing safety and 25% ALT reduction in NAFLD subjects but no significant liver fat reduction vs placebo. CohBar dissolved and CB4211 development is discontinued. Community-discussed protocol: 5 mg subcutaneously every 5 days for 20 days (4 injections). All community dosing is anecdotal and unvalidated.
Reported side effects
From community self-reports. Not from controlled studies.
CB4211 analog trial reported no serious adverse events but noted persistent injection site reactions (painless subcutaneous lumps). Community reports include heart palpitations, injection site irritation, insomnia, fever, and mild fatigue. FDA has stated it has not identified any human exposure data for MOTS-c. Contradictory preclinical signals exist regarding cancer — some data suggests anti-cancer properties while other data raises concerns about potential promotion of prostate and breast cancer.
Regulatory status
FDA (United States)
Not approved. FDA Category 2 bulk drug substance since September 2023 — identified as posing significant safety risks; compounding prohibited under 503A and 503B. HHS Secretary announced potential reclassification of ~14 Category 2 peptides on Feb 27, 2026, but no formal FDA action published as of March 16, 2026.
Health Canada
Not authorized as a therapeutic product. No DIN assigned. Not submitted.
WADA (Competitive Athletes)
Explicitly prohibited under S4.4 (Metabolic Modulators) as an activator of AMPK — specifically named alongside AICAR on the Prohibited List. Banned at all times (in- and out-of-competition). Additionally falls under S0 as a non-approved substance. Listed since 2024.
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