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Introduction: Spermidine, a naturally occurring polyamine found in various foods, has been linked to enhanced autophagy
and has shown potential cognitive benefits in previous human studies. This mini-review aimed to evaluate the evidence on
spermidine’s effect on the adult population’s cognitive functions.
Methods: Randomized clinical trials, controlled cohort/cross-sectional, and controlled before-after studies assessing
spermidine consumption/supplementation compared to placebo, non-placebo comparators, or regular diet evaluating
cognitive function in adults were included. A comprehensive search in MEDLINE, EMBASE, and CENTRAL yielded
1726 records. After duplicate title/abstract and full-text screening, 17 studies were assessed for eligibility, and three were
included in the review.
Results: All studies were randomized controlled trials in adults aged 60-96. Doses of spermidine supplementation ranged
from 0.9mg to 3.3mg. Wirth 2018 (30 participants) and Pekar 2021 (85 participants) showed an improvement in cognitive
performance after three months of spermidine supplementation measured with the Mnemonic Similarity Task (MST) and the
CERAD-Plus test, respectively. Schwarz 2022 (100 participants) did not find a significant change in memory performance
after 12 months of spermidine supplementation compared to placebo measured with MST. Two studies were at high risk of
bias, while one study was judged to have a low risk of bias using the Cochrane risk-of-bias tool for randomized trials 2 (RoB
Conclusion: Current evidence of the effect of spermidine on cognitive function shows inconsistent results based on a few
studies with low spermidine doses and a small number of participants. Further evidence is needed to assess its actual effect.