This preprint makes a case for considering spermidine a double-edged sword, with its impact depending on host genetic background (APOL1 variants) and cellular context (e.g., IFNγ-primed macrophages). While it continues to hold promise as a geroprotective agent, these findings provide a cautionary note for precision supplementation in populations at risk for APOL1-mediated kidney and cardiovascular disease.
Personally, having only a 23andme genetic profile, it looks like I am unable to be certain about APOL1.