Spermidine — Polyamine / autophagy inducer
Spermidine is a naturally occurring polyamine found in wheat germ, soybeans, cheese, mushrooms, and green peas. Endogenous polyamine levels decline with age. Spermidine is the most potent known natural inducer of autophagy ('cellular self-cleaning') via inhibition of EP300 acetyltransferase, leading to deacetylation of autophagy proteins (ATG proteins). Observational data: higher dietary spermidine associated with reduced cardiovascular mortality (Kiechl 2018, n=829, 20-year follow-up). Mechanism also involves epigenetic regulation of gene expression, anti-inflammatory effects, and telomere elongation. Nattō (fermented soybeans) and aged cheese are richest dietary sources.
Overview
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Compound Class
Polyamine / autophagy inducer
Mechanism of Action
Spermidine is a naturally occurring polyamine found in wheat germ, soybeans, cheese, mushrooms, and green peas. Endogenous polyamine levels decline with age. Spermidine is the most potent known natural inducer of autophagy ('cellular self-cleaning') via inhibition of EP300 acetyltransferase, leading to deacetylation of autophagy proteins (ATG proteins). Observational data: higher dietary spermidine associated with reduced cardiovascular mortality (Kiechl 2018, n=829, 20-year follow-up). Mechanism also involves epigenetic regulation of gene expression, anti-inflammatory effects, and telomere elongation. Nattō (fermented soybeans) and aged cheese are richest dietary sources.
Regulatory Status
OTC dietary supplement. Not FDA-reviewed for any indication.
Evidence Level
Emerging — Phase 2 data (n=100, SMNutrition trial 2021) and epidemiological associations. No Phase 3 longevity RCT. Strong preclinical autophagy induction evidence.