Supplement Scholar
Mitochondrial

MOTS-c

Research compound. This is not a dietary supplement. Unless it is identified as an approved prescription drug, it is not approved by the FDA for human use. This page summarizes published research for education only; we do not sell it or link to sellers.

MOTS-c. A mitochondrial-derived peptide that signals systemic metabolic regulation, insulin sensitivity, and exercise capacity.

How it works. Activates AMPK and modulates folate-methionine cycles, improving glucose uptake, fatty-acid oxidation, and stress resistance in muscle and other tissues.

What the research supports. 3 graded claims. Strongest: Anecdotal improvements in stamina and metabolic flexibility (preclinical).

Hormonal impact. Effects on Insulin sensitivity, Leptin, Adiponectin, Cortisol & sex hormones.

Side effects and interactions. 1 medication interaction listed. Serious: Long-term human safety is not established.

Stacking. Pairs well with Regular resistance and aerobic training. Avoid combining with Hypoglycemia-prone individuals.

Common forms. Available as Subcutaneous injection.

Community. Experiences from people who have tried MOTS-c. Anecdotes are not medical advice.

MOTS-c. A mitochondrial-derived peptide that signals systemic metabolic regulation, insulin sensitivity, and exercise capacity.

16-residue chainC101H152N28O22S2 · 2174.6 g/mol

What it is

MOTS-c is a 16-amino-acid peptide encoded within mitochondrial DNA, acting as a signaling molecule that influences metabolic homeostasis.

How it works

Activates AMPK and modulates folate-methionine cycles, improving glucose uptake, fatty-acid oxidation, and stress resistance in muscle and other tissues.

Pathways

  • AMPK activation
  • Folate cycle modulation
  • Insulin signaling

Effects

  • ↑Insulin sensitivity (preclinical) increases
  • +Exercise capacity and metabolic flexibility supports
  • ↓Diet-induced fat gain in animal models decreases

What the research supports

Anecdotal improvements in stamina and metabolic flexibilitypreclinical
Preclinical reductions in age-related insulin resistancepreclinical
May complement training adaptationspreclinical

Strong: consistent results across large trials or meta-analyses. Moderate: several trials, mostly positive. Limited: small or mixed studies. Preclinical: animal or cell research only.

Hormonal impact

↑Insulin sensitivityincreases
~Leptinmodulates
↑Adiponectinincreases
=Cortisol & sex hormonesstabilizes

Side effects & interactions

Common side effects

  • Injection-site reaction
  • Mild fatigue

Serious

  • Long-term human safety is not established

Medication interactions

Antidiabetic medicationsmoderate

Theoretical additive effect on glucose lowering.

Check any supplement–medication combination with your pharmacist before starting.

Combines with

Pairs well

  • Regular resistance and aerobic trainingSynergistic with mitochondrial adaptation.

Avoid combining

  • Hypoglycemia-prone individualsMonitor glucose closely.

Common forms

  • Subcutaneous injection

Discussion

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