Examining Spermidine's Impact on Memory Performance in Older Adults at Risk for Dementia: A Randomized Controlled Trial

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- Updated by Jody Mullis

  • The study investigated the impact of nutritional spermidine on memory performance in older adults at risk for Alzheimer's disease.
  • The trial showed improvement in memory performance and mnemonic discrimination ability in the group treated with a spermidine-rich plant extract supplement as opposed to the placebo group.
  • Spermidine supplementation's beneficial effects could stem from its stimulation of neuromodulatory actions in memory systems.
  • To confirm the findings and investigate the detailed neurophysiological mechanisms, follow-up Phase IIb randomized controlled trials are proposed.
  • The results highlight the potential of spermidine in delaying or preventing cognitive aging in people at risk of dementia.

Spermidine Study 2018


In 2018, the Cortex journal published a groundbreaking study titled "The effect of spermidine on memory performance in older adults at risk for dementia: A randomized controlled trial." The study aimed to investigate the potential cognitive benefits of spermidine supplementation in an aging human population at risk of Alzheimer's disease. Spermidine, a natural polyamine, is known for enhancing autophagy – a cellular clean-up process, and preventing memory loss in aging models. The study can be found here.


The study followed a three-month randomized, placebo-controlled, double-blind Phase IIa pilot trial design. The cohort consisted of 30 participants, ranging from 60-80 years of age, all carrying some subjective cognitive decline but were otherwise cognitively intact. The researchers administered the group with a spermidine-rich plant extract supplement and evaluated the effects using the behavioral mnemonic similarity task pre and post-intervention.


The primary outcome, memory performance, showed a moderate enhancement in the spermidine supplement group versus the placebo group at the end of the three-month period. The contrast mean (.17) suggested that the improvement resulted from the spermidine supplement. Furthermore, mnemonic discrimination ability—an important component of memory that distinguishes between similar experiences—also improved in the spermidine-treated group, indicating a medium effect size. This enhancement was absent in the placebo-treated group.


The pilot study results infer a positive impact of spermidine on memory performance in older adults in the pre-dementia stage— those who experience subjective cognitive decline. The researchers theorize that the beneficial effect might stem from spermidine's stimulation of neuromodulatory actions in the memory system. However, the precise neurophysiological mechanisms remain unascertained. Therefore, it is recommended that follow-up Phase IIb randomized controlled trials be conducted to validate spermidine's therapeutic potential and delineate the potential mechanisms contributing to its action.


This study's results tap into an area that holds a lot of promise for delaying or preventing cognitive aging, including Alzheimer's and other forms of dementia.