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

Publication date: Available online 4 October 2018

Source: Cortex

Author(s): Miranka Wirth, Gloria Benson, Claudia Schwarz, Theresa Köbe, Ulrike Grittner, Dietmar Schmitz, Stephan J. Sigrist, Jens Bohlken, Slaven Stekovic, Frank Madeo, Agnes Flöel

Abstract

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

Participants with subjective cognitive decline (n = 30) 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 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 = 0.17, 95% confidence interval [CI]: -0.01, 0.35, Cohen's d = 0.77, 95% CI: 0, 1.53). Mnemonic discrimination ability improved in the spermidine-treated group with a medium effect size (mean difference = -0.11, 95% CI: -0.19, -0.03, Cohen's d = 0.79, 95% CI: 0.01, 1.55). A similar effect was not found in the placebo-treated group (mean difference = 0.07, 95% CI: -0.13, 0.27, Cohen's d = -0.20, 95% CI: -0.94, 0.54).

Discussion

Nutritional spermidine was associated with a positive impact on memory performance in older adults with subject cognitive decline. This 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 in the target population.

Trial registration

Registered in ClinicalTrials.gov with the Identifier NCT02755246.

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