MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA-c) is a 16-amino acid peptide encoded by mitochondrial DNA. Discovered in 2015, it functions as an "injectable exercise"—mimicing the metabolic effects of physical exercise by activating the AMPK pathway. Natural levels increase 11.9 times in muscle after exercise but decrease with age.

Main Benefits:

• Mimics the effects of exercise (exercise mimic)

• Increased physical endurance and exercise capacity

• Significant improvement in insulin sensitivity and glucose metabolism

• Prevention/reversal of insulin resistance and type 2 diabetes

• Weight loss and obesity reduction

• Increased mitochondrial health and biogenesis

• Preservation of muscle mass and homeostasis

• Protection against age-related physical decline

• Increased energy, reduced fatigue

• Reduction of systemic inflammation

• Improved cognitive function and memory

• Cardiovascular benefits

• Promoting healthy aging (healthspan)

Typical Dosages:

• Typical Dose: 5-10 mg, 2-3 times per week

• Administration: Subcutaneous injection (thigh, arm, abdomen)

• Timing: Preferably in the morning

• Frequency: 2x per week (more convenient than daily peptides)

Mechanism of Action:

During metabolic stress or exercise, MOTS-c translocates to the nucleus and regulates stress adaptation genes. It activates the Folate-AICAR-AMPK pathway: inhibits purine synthesis → accumulates AICAR → activates AMPK → increases glucose uptake and fat oxidation. It interacts with antioxidant elements (ARE) and activates NRF2. Targets: skeletal muscle, liver, adipose tissue, brain.

Clinical Evidence:

• Animals: Improved performance in young, middle-aged, and elderly rats. Prevented insulin resistance and diet-induced obesity.

• Humans: Exercise increases levels 1.6x during and 1.5x after. Levels are reduced in obese individuals and those with type 2 diabetes.

• Results: Weeks 1-2 (energy), Weeks 4-6 (physical performance)

Stacking:

• Fat Loss: MOTS-c + CJC-1295 + Ipamorelin

• Performance: MOTS-c + Krill Oil + Ashwagandha

• Anti-Aging: MOTS-c + NMN/NR + Resveratrol

Side Effects:

• Generally well tolerated (naturally produced)

• Common: Local irritation, initial mild fatigue, changes in appetite

• Rare: Hypoglycemia, palpitations, insomnia, fever

Contraindications:

• Pregnancy/breastfeeding

• Active cancer

• Uncontrolled heart conditions

Legal Status:

• FDA: Experimental peptide, not approved for human use.

• WADA: PROHIBITED for professional athletes (Section 4 Prohibited List)

• Human use is off-label and experimental.

Important Note: MOTS-c is a promising experimental peptide for diabetes, obesity, and healthy aging. Complete clinical trials in humans are lacking. Use requires medical supervision. Prohibited in professional sports.