Creatine Supplementation in Preclinical Models Receiving Immune Checkpoint Inhibitor Therapy: A Systematic Review.
Level 5 - mechanism / opinion, no new human data
Systematic review of preclinical (animal/in vitro) studies with no human clinical data
PubMed 42255854 · doi:10.7759/cureus.108384
What was done
Authors conducted a systematic review evaluating the beneficial, neutral, or detrimental effects of creatine supplementation combined with immune checkpoint inhibitor (ICI) therapy across preclinical oncologic models. Out of 230 articles screened, 5 preclinical studies met inclusion criteria.
What was found
The abstract reports no numerical effect sizes or quantitative outcome data. Synthesized preclinical evidence indicates that creatine supplementation may improve antitumor responses when combined with PD-1 blockade by boosting CD8+ T-cell metabolic fitness (via SLC6A8 transport and phosphocreatine ATP buffering) and macrophage-driven inflammation. However, conflicting preclinical findings showed potential creatine-associated metastasis in select tumor models.
Why it matters
Creatine is widely used for athletic performance, but these preclinical findings suggest it could act as a metabolic adjuvant for cancer immunotherapy. However, contradictory signals regarding metastatic risk demonstrate that clinical translation requires extreme caution.
Limits
The evidence is restricted entirely to 5 preclinical laboratory models, with zero human clinical data available. Specific tumor types, dosing regimens, and quantitative survival or tumor reduction metrics were not reported in the abstract.