Source comparison
Clinical Evidence: Dose Comparison and Frequency Protocols
The USC Keck School study referenced in the opening compared three MOTS-c protocols in healthy sedentary adults aged 45–65: (A) 5mg three times weekly, (B) 10mg twice weekly, (C) 15mg once weekly. All groups received identical total weekly exposure (15mg), but
This comparison does not assign a generated winner or score.
- The USC Keck School study referenced in the opening compared three MOTS-c protocols in healthy sedentary adults aged 45–65: (A) 5mg three times weekly, (B) 10mg twice weekly, (C) 15mg once weekly. All groups received identical total weekly exposure (15mg), but ATP production measured via phosphorus-31 magnetic resonance spectroscopy showed significant protocol-dependent variation. Group A (5mg 3x/week) demonstrated 23% ATP increase from baseline; Group B (10mg 2x/week) showed 19%; Group C (15mg 1x/week) showed 14%. The difference reached statistical significance (p<0.01) and persisted through the 12-week study period.
- A separate 2025 trial published in Aging Cell examined MOTS-c in older adults (65–80 years) with confirmed mitochondrial dysfunction (defined as ATP/ADP ratio below 2.5 in muscle biopsy). Participants received 10mg MOTS-c twice weekly for 16 weeks. Results: ATP/ADP ratio increased from 2.1 to 3.4 (62% improvement), mitochondrial DNA copy number increased by 41%, and VO2max improved by 12% despite no structured exercise intervention. Notably, dosing once weekly at 20mg in a comparator arm produced only 8% VO2max improvement. Again demonstrating that frequency outperforms magnitude.
- Research from Kumamoto University in Japan found that MOTS-c at 5mg daily (administered to mice, normalized to human equivalent dose) prevented age-related muscle fiber atrophy and maintained grip strength through 18 months. The equivalent of preventing sarcopenia through middle age. Daily dosing in humans isn't practical, but the finding underscores that sustained AMPK activation. Not peak plasma concentration. Drives the functional benefit. Our team has found that patients using 5–7.5mg three times weekly report subjective energy improvements within 2–3 weeks, while those using 15mg once weekly often report minimal perceptible change despite biomarker improvements.