The effect of spermidine on memory performance in older adults at risk for dementia: A randomized controlled trial

Introduction Nutritional intervention with the natural polyamine spermidine, an autophagy-enhancing agent, can prevent memory loss in aging model organisms. This is the first human study to evaluate the impact of spermidine supplementation on memory performance in older adults at risk for the development of Alzheimer's disease. Methods Cognitively intact participants with subjective cognitive decline (n = 30, 60–80 years of age) were included in this three-months, randomized, placebo-controlled, double-blind Phase IIa pilot trial with a spermidine-rich plant extract supplement. Effects of intervention were assessed using the behavioral mnemonic similarity task, measured at baseline and post-intervention visits. Data analysis was focused on reporting and interpreting effectiveness based on effect sizes. Results Memory performance was moderately enhanced in the spermidine group compared with placebo at the end of intervention [contrast mean = .17, 95% confidence interval (CI): −.01, .35, Cohen's d = .77, 95% CI: 0, 1.53]. Mnemonic discrimination ability improved in the spermidine-treated group with a medium effect size (mean difference = −.11, 95% CI: −.19, −.03, Cohen's d = .79, 95% CI: .01, 1.55). A similar effect was not found in the placebo-treated group (mean difference = .07, 95% CI: −.13, .27, Cohen's d = −.20, 95% CI: −.94, .54). Discussion In this pilot trial, nutritional spermidine was associated with a positive impact on memory performance in older adults with subject cognitive decline. The beneficial effect might be mediated by stimulation of neuromodulatory actions in the memory system. A follow-up Phase IIb randomized controlled trial will help validate the therapeutic potential of spermidine supplementation and delineate possible neurophysiological mechanisms of action. Trial registration Registered in ClinicalTrials.gov with the Identifier NCT02755246 .