NAD+ activates SIRT1, which deacetylates Beclin-1 and ATG5 — autophagy proteins that EP300 inhibits via acetylation. Spermidine and NAD+ therefore work on the same autophagy substrates via opposing enzyme activities (EP300 adds acetyl groups; SIRT1 removes them). This creates elegant synergy: spermidine removes EP300's inhibitory acetylation; NAD+/SIRT1 reinforces deacetylation.
Is taking both spermidine and NMN redundant?
Not redundant — they work on the same endpoints (autophagy) through genuinely different mechanisms. Think of it as activating autophagy via two independent power switches. Each adds incrementally; neither makes the other unnecessary.
What order should I take spermidine and NMN?
Both can be taken simultaneously with or without food. Some practitioners prefer NMN in the early morning (aligned with circadian NAD+ rhythms) and spermidine with breakfast. There is no established optimal sequence.