MOTS-c: Side Effects & Safety

MOTS-c is a naturally occurring mitochondrial-derived peptide, present in human cells as part of normal mitochondrial signaling. This endogenous origin suggests inherent compatibility with human biology. Preclinical studies have reported a favorable safety profile, though large-scale human clinical trials are still limited.

• Injection site reactions: Mild redness or irritation at the subcutaneous injection site
• Mild GI effects: Occasional nausea or decreased appetite, consistent with metabolic activation
• Hypoglycemia risk: As MOTS-c enhances glucose uptake independently of insulin, individuals on diabetes medications should be aware of additive hypoglycemic effects
• Fatigue: Transient fatigue reported by some during the first few days, potentially related to metabolic adaptation

• Human clinical trial data is still emerging — most safety data comes from animal studies
• Long-term effects of sustained AMPK activation via exogenous MOTS-c are not fully characterized
• Potential interactions with diabetes medications (metformin also activates AMPK)
• Not studied in pregnant or breastfeeding individuals

• Type 1 diabetes or insulin-dependent diabetes (risk of hypoglycemia)
• Concurrent use of metformin or other AMPK activators without medical supervision
• Pregnancy and breastfeeding

Return to the MOTS-c overview for general information.