Evidence Level
Spermidine is a polyamine that has been studied for its potential role in promoting longevity and improving healthspan. The Bruneck Study (Eisenberg et al., 2016) identified an inverse relationship between dietary spermidine intake and mortality, suggesting its cardioprotective and lifespan-extending properties. A review by Madeo et al. (2018) emphasized spermidine's role as a potent inducer of autophagy, achieved through the inhibition of EP300 acetyltransferase, leading to deacetylation and activation of autophagy-related proteins.
Recent studies have explored the effects of spermidine supplementation in humans. Wirth et al. (2018) conducted the first placebo-controlled trial, demonstrating cognitive benefits in older adults with subjective memory decline. A pilot study by Bruno et al. (2025) found that 3.3 mg/day of spermidine from rice germ extract increased autophagy biomarkers and improved cardiometabolic health. However, Keohane et al. (2024) reported that 40 mg/day of high-purity spermidine supplementation in older men had no significant effects on polyamine levels or safety outcomes over 28 days.
While epidemiological and mechanistic evidence supports spermidine's benefits, large-scale interventional trials specifically measuring lifespan or healthspan outcomes remain necessary.