Source comparison
Dosing Protocols: Animal Equivalence vs Human Reality
Animal dosing in MOTS-c research typically ranges from 5mg/kg to 15mg/kg administered intraperitoneally (directly into the abdominal cavity). For a 25-gram mouse, that's 125–375 micrograms per dose. Human equivalent dose (HED) calculations. The FDA-approved fo
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- Animal dosing in MOTS-c research typically ranges from 5mg/kg to 15mg/kg administered intraperitoneally (directly into the abdominal cavity). For a 25-gram mouse, that's 125–375 micrograms per dose. Human equivalent dose (HED) calculations. The FDA-approved formula for translating animal doses to human protocols. Suggest a human dose of approximately 0.4mg/kg to 1.2mg/kg based on body surface area correction. For a 70kg adult, that translates to 28mg to 84mg per dose. Yet no human trial published through 2026 has used doses above 10mg per administration, and most protocols use 5mg three times weekly.
- The discrepancy exists because subcutaneous bioavailability in humans differs from intraperitoneal injection in mice. Mice absorb peptides rapidly through the peritoneal membrane with minimal first-pass metabolism. Humans absorbing MOTS-c subcutaneously experience slower, sustained release with partial enzymatic degradation at the injection site. A 5mg human dose may produce plasma concentrations comparable to a 10mg/kg mouse dose when absorption kinetics are accounted for. Our experience working with researchers sourcing peptides for clinical studies consistently shows this pattern. The 'equivalent' dose based purely on body weight overestimates what's needed to saturate the relevant receptors in humans.
- Timing matters as much as dose. Animal studies dose daily or every other day because rodent metabolic cycles are compressed. Human protocols using three-times-weekly dosing (Monday, Wednesday, Friday) produce comparable cumulative effects to daily dosing in pilot comparisons, likely because MOTS-c's half-life in humans is approximately 6–8 hours, but its downstream metabolic signaling. AMPK activation and mitochondrial gene expression. Persists for 48–72 hours after a single dose. Dosing more frequently doesn't accelerate the mitochondrial biogenesis timeline; it just maintains the signal. For human research applications, the MOTS-C Nasal Spray format offers an alternative delivery route that bypasses first-pass metabolism and may improve consistency.