Exogenous creatine supplementation promotes tumor metastasis via megakaryocyte creatine kinase B-STAT5B signaling.
Level 5 - mechanism / opinion, no new human data
Preclinical animal and mechanistic study with surrogate biomarker measurements in healthy human volunteers
PubMed 42449108 · doi:10.1038/s41467-026-74639-z
What was done
Researchers investigated the effects of exogenous creatine supplementation on tumor metastasis and platelet activation across mouse models and healthy human volunteers. They examined underlying pathways using unbiased phosphoproteomics, megakaryocyte-specific knockout mouse models (targeting the creatine transporter Slc6a8 or Stat5b), and pharmacological inhibition of STAT5.
What was found
The abstract reports no numerical values, effect sizes, or sample sizes. Exogenous creatine supplementation increased megakaryocyte creatine levels and upregulated creatine kinase B (CKB), which induced non-canonical STAT5B phosphorylation and activated platelet functional genes. Megakaryocyte-specific deletion of Slc6a8 or Stat5b, as well as STAT5 inhibition, eliminated creatine-induced platelet hyperactivity and blocked metastasis in mice. In healthy volunteers, creatine supplementation resulted in hyperactive peripheral platelets.
Why it matters
This work identifies a mechanistic pathway linking dietary creatine intake to megakaryocyte-driven platelet activation and cancer metastasis in preclinical models. It suggests that creatine supplementation might carry previously uncharacterized oncologic risks and identifies megakaryocyte creatine metabolism as a potential anti-metastatic target.
Limits
The abstract reports no sample sizes (n = ?), dosing details, or numerical statistics. Human evidence is restricted to surrogate markers of platelet activation in healthy volunteers rather than observed clinical metastasis outcomes.