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MOTS-C side effects and results in studies

The studied benefits of MOTS-c come from animal and cell work: in the original mouse study it prevented diet-induced obesity and insulin resistance, and later rodent studies reported less tissue injury in lung, joint and heart models. Two mouse studies reported no notable or systemic toxicity, but no human trial of added MOTS-c appears in these records.

Adverse events reported

EventAs reportedSource
Toxicity in vitro and in vivoNo notable toxicity reported in HBV-infected mice and cellsLin C et al.
Systemic toxicityNo systemic toxicity reported in the ovarian cancer mouse modelYin Y et al.
Adverse events in peopleNot reported: no controlled human trial of added MOTS-c in these recordsLee C et al.

Outcomes measured

OutcomeResult as reportedSource
Insulin resistance and obesity (mouse)MOTS-c treatment prevented age-dependent and high-fat-diet-induced insulin resistance and diet-induced obesityLee C et al.
AMPK activation (skeletal muscle)MOTS-c inhibited the folate cycle and de novo purine biosynthesis, leading to AMPK activationLee C et al.
Nuclear gene regulation under stress (cells)MOTS-c translocated to the nucleus and regulated antioxidant response element genes after glucose restrictionKim KH et al.
Lung ischaemia-reperfusion injury (rat)Exogenous MOTS-c reduced oxidative damage, inflammation, lung injury and mortalityLi X et al.
HBV replication (mice and cells)50–70% inhibition of HBV replication alongside improved liver functionLin C et al.
Cartilage degeneration (mouse osteoarthritis)MOTS-c delayed articular cartilage degeneration on imaging and histologyLi K et al.
Myocardial injury markers (LPS sepsis model)Lower CK-MB, TnT and inflammatory cytokine mRNA; effect abolished by an AMPK inhibitorWu J et al.
Ovarian cancer growth (cells and mice)Reduced proliferation, migration and invasion in cells and an anti-tumour effect in vivoYin Y et al.

What the studies don't show

These results do not show that MOTS-c has any benefit in people; the human data only relate circulating MOTS-c levels to disease. The animal studies are mostly short, acute models, and the abstracts report safety only as an absence of notable toxicity rather than as measured adverse-event rates.