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Effects of Spermidine Supplementation on Cognition and Biomarkers in Older Adults With Subjective Cognitive Decline: A Randomized Clinical Trial

Schwarz C, Benson GS, Horn N, Wurdack K, Grittner U, Schilling R, Märschenz S, Köbe T, Hofer SJ, Magnes C, Wirth M, Madeo F, Flöel A, et al.

JAMA Network Open 2022 5(5):e2213875

Bibliography

PubMed: PMID 35616942
PubMed Central: PMC9136623
DOI: 10.1001/jamanetworkopen.2022.13875
Funding: Supported by German institutional and academic research grants (Charité — Universitätsmedizin Berlin and collaborating institutions); full disclosure in the original publication.
Competing interests: None declared in the published article.

Study snapshot

Design	12-month randomised, double-masked, placebo-controlled Phase 2b trial (SmartAge)
Model	Older adults (60-90 years) with subjective cognitive decline
Sample	100 randomised (51 spermidine, 49 placebo); 89 completed
Intervention	Spermidine-rich wheat-germ extract supplement, 0.9 mg spermidine/day, vs placebo (microcrystalline cellulose)
Duration	12 months
Endpoints	Mnemonic discrimination performance (primary); Secondary neuropsychological, behavioural, and inflammatory biomarkers

What the study showed, in plain terms

This was the proper, full-scale follow-up to an earlier small positive pilot. Over 12 months, spermidine supplementation did not improve memory performance compared with placebo. Some exploratory secondary measures — inflammation and verbal memory — showed possible benefit, but these need confirmation in future trials.

Key findings

In this 100-person, 12-month RCT, spermidine supplementation (0.9 mg/day from wheat germ extract) produced no significant difference from placebo on the primary outcome, mnemonic discrimination memory performance. Exploratory analyses suggested possible benefits on inflammation and verbal memory, but these were not the primary endpoint and require independent confirmation.

What this study can and cannot tell us

The primary cognitive outcome was null, directly contradicting the positive signal from the earlier Wirth et al. 2018 pilot trial. The dose used (0.9 mg/day, from a food-derived extract) is far lower than doses used in some other spermidine trials, which may partly explain the null result. Exploratory secondary findings should be treated as hypothesis-generating, not confirmatory.

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