Spermidine

Natural polyamine that induces autophagy through inhibition of the acetyltransferase EP300 (p300), leading to deacetylation of core autophagy proteins including ATG5, ATG7, ATG12, and Beclin-1. Promotes mitophagy (selective clearance of damaged mitochondria), reduces age-related inflammation, and enhances proteostasis. Endogenous spermidine levels decline with age. Dietary sources include wheat germ, aged cheese, mushrooms, and fermented soy.

Half-life

Variable (rapidly metabolized and incorporated into polyamine pools)

Bioavailability

~80% (oral, rapidly absorbed in small intestine)

Route

oral

Evidence tier

T2 — Single-RCT or mechanistic

Optimization pillars

anti-aging · cellular-health

References

4 peer-reviewed

Dose ranges

Three tiers ordered by aggressiveness. Tier chips on every OPTIMIZE intervention let you filter the catalog by your evidence tolerance.

conservative

1 mg/day

Dietary-level supplementation

moderate

2–3 mg/day

Enhanced autophagy induction

aggressive

5–6 mg/day

High-dose protocol (clinical trial dosing)

Monitoring

hs-crp
lipid-panel
fasting-glucose
hba1c
alt
ast

Contraindications

active-cancer-polyamine-dependent
concurrent-eflornithine
pregnancy

References

PMID:19801985Induction of autophagy by spermidine promotes longevity — Nat Cell Biol, 2009
PMID:27841876Cardioprotection and lifespan extension by the natural polyamine spermidine — Nat Med, 2016
PMID:30462961Higher spermidine intake is linked to lower mortality: a prospective population-based study — Am J Clin Nutr, 2018
PMID:34375542Spermidine supplementation and memory performance in older adults at risk for dementia — Cortex, 2021

Notes

Spermidine is autophagy in a capsule. The 2009 Nature Cell Biology paper showed it extends lifespan across yeast, worms, flies, and mice through EP300 inhibition and autophagy induction. The 2016 Nat Med paper added cardioprotection. The 2018 prospective cohort data linked higher dietary spermidine intake to lower all-cause mortality in humans. The mechanism is distinct from mTOR inhibition (rapamycin) — spermidine works through the acetyltransferase pathway, making it potentially complementary rather than redundant. The human cognitive trial showed memory improvement in older adults at risk for dementia. Wheat germ extract remains the most concentrated natural source.

This is not medical advice

Discuss with a licensed clinician before starting, stopping, or changing any compound. This page documents what the research literature describes — it is not a prescription.

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